Well, good morning, everyone. Welcome to a buprenorphine course. We're very pleased to see you today. As I'm sure you're aware, the waiver is no longer required, and we've been curious as to whether anyone was going to come to the courses anymore. So it looks to me like we've got a really robust crowd of people, and they're going to be streaming the course at the same time, so I don't know how many people are watching us remotely, but welcome. Very pleased to see you here. I would really hope that we can have a robust discussion-type learning environment. These courses, I think, go best if you ask questions and you participate. Give us a little time to get through our slides, but please feel free to jump in if you have questions, and we will try to leave time during the course of the day to have discussions. I hope you all have gotten a chance to copy this so that you can participate in the live polling. Okay. Faculty, myself, I'm John Renner from Boston University. Petrus DeLunas, who is the incoming president of the APA, will be joining us briefly later in the morning to do one of the cases. I'm joined today by D.C. Park, who is also at Boston University, and Andy Saxon from the University of Washington. We have a group of, I think, very seasoned buprenorphine experts with us, so I hope that we'll be able to lead you on a good course through the day here. We're going to start out-well, we've got to begin with the definition of addiction. I'm sure that this is not news for this audience. Addiction is a chronic relapsing brain disorder with functional changes in brain circuits through reward, stress, self-control, impaired. Addiction is treatable. I think the best treated by thinking about it from a public health model and seeing as a chronic illness, with looking at the genetics, environmental influences, life experiences that affect things, and think particularly in terms of prevention, early identification is one of the important parts of our job. We're going to begin with sort of some background material, a little housekeeping first. I want to have everyone please be sure to sign in. Even without the waiver, I think we're all going to be required to do a certain amount of training the next time we get our DEA, so you may need to be able to document that you've done that. So we need you to sign in. We'll have course evaluations. We ask you to please turn off your cell phones. Any questions at the beginning? Yes? Yes? Where's the sign-in? It should be back at the check with Violet. She should have it. Do you know where it is, Violet? Here. What? What was the question? Where the sign-in sheet is. Oh, it should have been just when you got scanned in, yeah. Okay. Okay. We're going to have a combination of lecture presentations and then case discussions. They'll be scattered during the day. And as I said before, I hope that we have robust discussions both at the cases and after the lectures. This is a general overview of what we're doing. We're going to give a little background information first. We're then going to talk about the psychopharmacology. We're going to talk about patient evaluation. The first case will be a lawyer. After that, we probably will take a short break. We'll then talk about clinical use. I have two presentations on clinical use. Around that point, we'll probably take a break for lunch. Second case is going to be about the teacher. We're going to do a presentation on evidence-based counseling. We're going to cover special topics, pain, psychiatric comorbidity, pregnancy, another case, a little bit on drug testing. And then at the end, I'm just giving you information about where you can get added resources. The goal of the course is to give you information on the pharmacology and the clinical use of medications with assisted treatment for opiate use disorder. This is clearly a buprenorphine course. SAMHSA and the DEA have requested that we cover the other medications that are used in treating addiction. So, during various times during the day, you'll see we may make some references and give some information about methadone and naltrexone in a little bit more detail. But the primary focus is going to be on buprenorphine. Let me do this before. Okay. This slide gives you a sense of what's the background of addictions. How much of it is related to genetic problems? How much of it is environmental? It's not quite 50-50, but genetics play a very major part having to do with what type of opiate receptor peoples have, dopaminergic tone, transmitters, intercellular signals. We're still learning. We understand there are behavioral aspects of this. People who are high in terms of novelty-seeking, people who have low harm avoidance, people highly impulsive, and people with psychiatric disorders. These individuals are all more vulnerable to becoming dependent on substances. On the environmental side, parents, siblings, friends have a big influence. Interestingly enough, probably the older siblings may be the most influential in determining vulnerability to dependence. Adverse childhood experiences are very problematic. Other psychiatric disorders, the lack of positive life experiences. And then, again, the availability. You have to encounter the drug. You have to be in an environment where it's possible to get exposed to the drug, or else you may have had a prescription that exposed you. And in most cases, it's family and friends who become the initial conduits for the medication. How does this affect the country? The societal costs are well over $400 billion annually. The direct health care costs are over $120 billion annually. So this is very consequential in terms of the overall health picture in the United States. It affects the quality of our health, our educational correction systems. As I think we are all well aware, one of the unfortunate consequences of deinstitutionalization has been that large quantities of people with substance abuse problems have ended up in the criminal justice system. There are racist problems related to that. There are bias related to that. But a lot of the people that we serve are in the criminal justice system, or in and out of the criminal justice system, and we have to take that into consideration. We need to pay attention to preventive policies and practices that are going to reduce the harm and the cost of these problems. But remember, it's an acquired chronic illness, like type 2 diabetes. It can be managed, but we don't cure it. Unfortunately, we have medications that work very well to help manage it, and we have a very good sense of psychological interventions that are helpful. How does it affect the population? Eight to ten percent of the population are vulnerable. Lower percentage of women are affected, more percentage of men. But those numbers are leveling out, and I think that unfortunately the percentage of women becoming involved is going higher, and I think we're getting very close to the point where it will be quite equal. Depending on what medical setting you work in, you're going to see either large or very, very large numbers of people with substance abuse problems. It's about 20 percent in the typical primary care clinic, about 40 percent in general medical settings and people treated in hospitals, but well over 70 percent in emergency room or urgent care hospitals. And in some specialty hospitals, like if you work in a safety net hospital in a big city, if you work at the VA, you may see that 60, 70 percent of the people you see have had some issues with substances. So it should be a careful thing that is screened for everywhere. We need to learn how to make diagnoses carefully. We need to be careful about prescribing. Dentists need to be careful. You give these three days of meds after a dental procedure, maybe not 30. I think that lots of pain situations where I think we were very liberal for years in prescribing, I think we're learning we have to be much more conservative, and we have to learn other alternatives as ways to manage that. We really have done best, I think, by thinking about addictions from a public health perspective. We need to prevent the problem before it starts. That means careful prescribing. That means avoiding drugs. That means teaching people other creative ways to invest their lives, energies, and not become victims of substance abuse. And if it does occur, we need to treat it early. It's clear that the medications work, but you need it for a length of time. It often takes people years to become fully addicted, and it may take them years to recover. It's not a simple thing. If you're going to do a patient well, I think you need to commit to working with them over the long course. That may mean over several relapses, may mean taking them back in treatment, but that long-term continuity, I think, ultimately leads to success. We'll talk more about this as we go on later. But there's also a need for supportive monitoring, recovery services, AA and similar groups, NA, are quite powerful if they're used correctly. And some combination between the supportive groups and medication are probably going to be most effective for most people. And I think you need to be aware that there are well over 20 million people in the United States who are in recovery. I think because of stigma, people don't walk around and say, gee, I'm a recovering alcoholic or I'm a recovering opiate addict. They tend to be invisible. They tend to lead their lives in very productive ways, and you don't even know that history. But they are there. And I think they are a reason for us to be optimistic about the work that we do. So let's go back a little bit of history. Opiates are probably the longest drug that has been available to humans, been available for many thousands of years. It really became a problem more in the 19th century. And that sort of crossed, intersected, if you will, with certain technological changes. The availability of morphine and heroin, so more potent forms of the drug, were now marketed. And in the 19th century, you're aware that they were marketed for all sorts of things that we would not use them for today. But that was coincidental with the invention of the hypodermic syringe. So we now had mechanisms for delivering higher potency drugs very rapidly into the brain. That became a very obvious problem after the Civil War, with people who were injured in the war produced a large number of people who were addicted. But the average addict in the latter part of the 19th century was a white woman farmhouse wife. People don't know that. They don't recognize how much is ingrained, if you will, in our culture. And there's always been prejudice about who's addict. If you talked to people in the 19th century, you would have heard about opium dens, and the people would have been looking at Asians who had come to the country. Well, that wasn't really where the problem was. The problem was in the indigenous population. And it's still widespread. Things changed with the Harrison Act in 1914. Prior to that, treating opiate-dependent people was a fairly major part of medicine. It's after the Civil War, maintain people on morphine if they needed it. And that went on for many, many years. But it came to an end, and I think there's a very interesting but more stigma play at this point. But I think it came to an end with the Harrison Act, which basically made it illegal to provide opiates to someone who was addicted to opiates. And after a few years, medicine basically washed their hands of really getting engaged in this treatment. And unfortunately, we've now had four to five generations of younger physicians who have never been exposed to the model of treating people in the medical system if they have opiate dependence. And ultimately, large numbers just got transferred into the criminal justice system. So I think we're hoping to reverse that pattern. This slide gives you some idea of some of the milestones more recently in the world of opiate addiction treatment. In 1970, methadone was approved for detoxification, then followed for maintenance treatment. In 1974, the first opiate treatment programs, which we commonly call methadone clinics, were structured. In 84, oral naltrexone was approved for treating alcohol. In 2000, the people looked at the problem with methadone treatment. I think methadone clinics never covered more than about 10 percent of the opiate addicts in the country. And they were siloed from the rest of medicine. So efforts were made to find a medication that would be effective for treating opiate addiction but could be instituted within the average doctor's office. And buprenorphine fit that bill. It was approved under the data 2000, which is the legislation that made it legal to use buprenorphine under certain conditions, and at that point required training. In 2002, buprenorphine was approved by the FDA for treatment. The next major change was the extended release naltrexone, which was much more effective than the oral naltrexone. The CARA Act in 2016 expanded the number of clinicians beyond physicians so nurse practitioners were able to prescribe. And then we get to more recent points where I think the government has basically loosened things up. We got to the point in 2018 where there were broader prescribing authority for different disciplines, loosening the requirements in terms of the number of people that could be treated by any one clinician. And finally in 2021, the elimination of the waiver. So we're getting towards the end of 2022, the waiver was eliminated, the number of patients you can treat was eliminated. So it was treated almost like any other medication that we normally use. And the only thing that is still supposedly going to be a requirement is an eight-hour training, which is what this course would do, which every physician in the country who holds a DEA license will need to have, unless they're board-certified in addiction medicine or addiction psychiatry or have taken a course like this. So it's an effort to kind of expand the treatment population broadly. And I'll give you a little bit more detail on the legal underpinnings. I'll go through some of this because I think it is not particularly relevant right now. But dated 2000, which was the law that initiated these changes with buprenorphine, any drug that was either in Schedule 3, 4, or 5 that was approved by the FDA for treating opiate use disorder could be used. It set limits beginning, in those days, first you could only treat 30 patients and then it was expanded to 100 and then to 275. So they gradually expanded the number you could do it. They also gradually expanded methadone clinics as settings where people could use it. And then in 2022, they eliminated the waiver and these various constraints on practice. In 2013 was the beginning of the time when methadone clinics could dispense buprenorphine in the methadone clinics. But initially, clinicians were required to follow the same controls of methadone with buprenorphine. So it really limited their flexibility in using buprenorphine. They basically have loosened that and now I think particularly with COVID, I think we've seen that it is possible to operate both methadone clinics and buprenorphine practices with much less control than was present in the past. And so far, this seems to be working pretty well. At least there have been no major identified negative sequelae of these changes. Now this slide, I think, is very important because it really gives you a visual picture of the range of goals for treatment. And you can see on one end it's harm reduction, on the other end we have talked about sustained recovery. So what does that mean? That means it is acceptable and reasonable to engage people in treatment who may not be fully committed to making big changes or even to completely stop what they're using. And I think we're still struggling as a society what the parameters of that are, what is limited. Clean needle sites, safe injection sites, are they acceptable? They are some places. They are not in other places. So we're struggling with what the harm reduction model looks like. Can people stay in harm reduction only if they're committed to eventually move into recovery models? It's not clear. I think in some cases or situations, people are working very hard to get everybody into harm reduction and not make many demands on them. At the other end, we have people who have really committed themselves to real recovery. They are much more common than what we've had in the past, if you will. But we're familiar with them from the models of AA and people in AA recovery. And these people get to a point, as I think you will see with buprenorphine, if you haven't already, they're back with their families, they're back in school, they're working full time, they're not using any drugs, they're becoming very productive citizens. And often that recovery has extended beyond their use of opiates. So they're not using any other drugs and they're very straightforward recovery people. A few of the people in that setting go on to give up buprenorphine on all medications and manage without any medications. We're still not at this point recommending that as standard practice. I think most of the time, the people we work with, I feel much safer that they stay on buprenorphine or methadone for the duration. They may be able to manage on lower doses and less frequent visits, but they stay on medication. I have a few people who've been off medication several years and continue to do well. We have no way to predict who could make that shift. So I think our standard recommendation at this point is that people stay on medication, either methadone, buprenorphine, or naltrexone, and they stay involved in behaviorally oriented treatment long term. But the ultimate goal is that they achieve a long term recovery. This slide shows you data from some studies which makes the point that, number one, you don't see instant recovery. And number two, you can expect gradual, slow, steady improvement if people stay in treatment. There isn't a quick fix. But as you can see from the top line, 100% of the people were engaged in treatment. At the end of the year, it was about 65%. So there were certain people who dropped out, which is true in any kind of treatment setting. But if you look at the green line, you can see how many people had negative urines, no opiates in their urine in the past month. In the beginning, only 50% of the people in treatment. So it wasn't everybody, and there were a lot of people who were still using regularly, and you will expect that in the people you see. But if you look at what happens, by the end of the year, we're getting close to almost 80% of people were coming in and had no opiates in their urines. So treatment was occurring and was possible, but not overnight, and it took time. But the longer people stay in treatment, the better they do. And one of the things that I would add to that is that relapses will happen. And the important thing is to know it's expected part of recovery, and the most important thing is you get them back into treatment as soon as possible after they've had a relapse. And if you can continue to work with them, continue to engage them over the long term, then I think you can see a success like this in your practice. This slide just compares death rates, and I don't think we have to overemphasize the point that we're in an epidemic of drug-related overdoses. Death rates in the green is for the general population. It's six times higher if they're people with an opiate use disorder and getting no treatment. If you add treatment, you simply get them in treatment. You drop the death rates, not down to where it is in the general population, but very close. You make a significant difference. You will save lives. This slide shows what's been described as the three waves in the rise of opioid overdose deaths. I suspect that this slide will probably be edited in the next couple of months as the course gets revised, but you can see you begin with the first wave, which was driven by OxyContin. It's sort of opioid pharmaceuticals causing the problem. In the second wave, it's response with increased heroin, which was driving the problem. In the third wave, you can see other synthetic opioids, think fentanyl, so that we've now got fentanyl pushing this major increase in opioid deaths, but what you need to look at is the bottom two lines because the use of heroin was beginning to drop off and the use of commonly prescribed opioids was beginning to drop off, so we were making some progress there. What this slide doesn't show is methamphetamine deaths, but I think we're still facing major problems in the country with methamphetamine deaths and fentanyl deaths, so we have a very serious problem, but I think changes in medical practice, better prescribing has reduced the use of other commonly prescribed opiates as a cause of this problem. How many people are in treatment? I don't really think the numbers in these slides are accurate. Probably over 400,000 people are currently in methadone treatment. There are well over 1,600 methadone treatment programs around the country. I think the numbers for buprenorphine are a little hard to get accurate readback, but I suspect it's several hundred thousand people on buprenorphine, and there are 23,000 people on naltrexone, the long-acting injectable naltrexone. That number is a problem. Naltrexone is a very effective drug and works well, but it's a problem getting people onto naltrexone. That's why the numbers are so low. It's hard to get them on, that's the first problem. If they get on, you can expect that they're probably gonna do just as well as people on buprenorphine do, but they don't stay in treatment. The average numbers from around the country suggest the retention in treatment with naltrexone runs around two months, maybe three months. So there's no recovery that I'm aware of that occurs in addiction problems if you get two months of treatment. So I think that one of the challenges for us is to figure out how to use naltrexone more effectively, both how to get people onto it, not lose them in the very beginning of the treatment, and how to keep them in treatment for long enough to achieve really good recovery. This slide is not particularly pertinent at this point. It just compares the caseloads of people who are prescribing. None of this is currently prescribed. There are major efforts going on now to eliminate the controls on buprenorphine, expand the education, get more people involved in treatment. I think we're gonna see increasing pressure to increase opioid treatment in medical schools. We're gonna see much more pressure in residencies and all disciplines to expose people to that. I think we're gonna relax the orders in terms of DEA training. Courses like this are probably gonna be not required as much, but to see a full room of people here today is very encouraging because I think, curiously enough, when we stop formally requiring the course, people are coming, and people seem to be more interested. I would be curious to get some feedback from you today when we talk about why you're here because you don't need to be here anymore. So I'm hoping that means that people are seeing the benefit of buprenorphine and interested in learning how to use it more effectively. So I've given you a fast snapshot of the continuing opioid epidemic, the history of medications that we have used. We're gonna talk today about how you use buprenorphine, a little bit on how you use naltrexone and methadone. We'll talk a little bit about AA and NA and various psychological interventions. I don't think we know exactly what the federal government is going to do with controls over the next year or two. Our understanding is that the requirements for training and the requirements for prescribing and the use of how we can start people remotely are under review and probably will not change in the next six months. But whether we will be able to do as much flexible prescribing that we did during COVID is unknown at this point. But I think people are recognizing we have a serious problem and we need to do more to take care of it. Any questions? Yes. Could you stand up and use the microphone because we're recording this so it would be helpful to use the microphone. I have patients who are on maintenance treatment with the buprenorphine for the last 15 or 18 years. Yes. Some of the patients chose to stop the treatment within a year, some of them five years. Most of them when they retire from the work they go off from the medicine because they feel they don't need this. I don't know how to decide who needs and who doesn't need. That's my first one question. Well, first of all, I'm very pleased to hear you report successful practice and how well it's going. I think that's one of the biggest questions. Maybe NIDA will have an answer to that in the next four or five years. But we really don't know. What we look at to predict in advance who's going to do well and who's going to stick with treatment or to predict who can safely stop buprenorphine or methadone. There's some suggestion that people may do better if they've never used needles, if they just got in trouble with opioid pharmaceuticals but didn't use needles. But that hasn't been well validated. Another question? The other question is people are on long-term treatment and the other question is people are on long-term maintenance. I don't do the urine drug screening quite often. I do it once a year at this point. I used to do once a month initially, then moved to once in three months, six months. Now it's once a year. Well, I don't think we can make a recommendation at this point because there's no data on that. I'm still seeing my patients once a month, maybe a few patients every other month. But there's no data to suggest what the good guidelines would recommend for people like you. And I think we have to make sure that people, you keep track of how you're doing, report it, so we can accumulate that data. I prescribe once a month and then I monitor the prescription monitoring program. I don't do the urine test that often. Well, let's move on to another question here, sir. Good morning, Dr. Renner. Thank you very much for this talk. I have two questions. One is when patients are on a long-term basis, five, six years, when they ask the physician, they don't want to be on this medication, how soon they can come off. Having known, I also had two other patients at the same week who had been abstinent for five years, came off that and then relapsed and then I had to restart, the same thing. So when people are asking, how do you help me to come off suboxone? How do I explain that? I think it's all individualized and we don't have the data. I find with some patients like that, if I reduce their dose a little bit, or they're having some side effects, they feel better and they stop talking about coming off. Other people insist that they're gonna go ahead and do it. And then when they start reducing their dose, they start getting sick and they start having more withdrawal symptoms. So we're looking at ways we can reduce doses and avoid the withdrawal symptoms and we may be getting there, but we haven't gotten there yet. But even without pain coming off or no withdrawal symptoms, is that safe? We don't know. I mean, they may be safe for a month or two, but we don't know whether they're gonna be safe for a year. I mean, we just don't have that data. There's one more question and then we'll have to move on. Thank you very much, Dr. Jena. I just want to ask you, I don't see my addiction colleagues using injectable naltrexone that often. And you also mentioned in your course today that injectable naltrexone is difficult to start and to initiate and to maintain. Could you share the light? Well, we're gonna talk about that later today. We'll go into more details about what the problems are about getting people on naltrexone. So we'll pass that on. Thank you. Okay, well, let's do our first polling question here. The DEA now allows for the prescription of all forms of formulations of buprenorphine, methadone, medications that are FDA approved for treatment of opiate use disorder in schedule three, four, or five, or oxycodone. So which of these do you think, A, B, C, or D, is the best way to describe when we're talking about specifically what medications you can use for treating opioid dependence? So we'll leave that up for a second and see if we can get some responses from the audience. If any of you are able to respond. Okay, I'm gonna go on here and see. Okay. Okay, so we've got 60% going with C. I think that's probably the right answer. There are some formulations that can only be used for pain, cannot be used for opioid use disorder of buprenorphine. Obviously, oxycodone is not approved for the treating of addiction. So I think this is what our first answer is here. Okay, second question. OBOT, that's office-based opioid treatment. Prescribers' requirements include which of the following? An active DEA registration, the use of specific medications for the treatment of a patient with OUD. There's no limit on patient panel size limits and all of the above. So think about that. So which answer would you suggest? And I would add to this, what is right now, based on the most current changes that the FDA and the DEA have made, what is the right answer to this? So you just need DEA, you only can use certain medications. You can treat any number of patients and they're all correct. Okay, I think we're all on the same page here. I think that's obviously the right answer right now. The DEA, with the newest changes, they've eliminated panel sizes. We can only use specific medications still that are approved. And you obviously have to have a DEA license. Okay, now I'm gonna turn this over to Dr. Satterthwaite. Okay, now I'm gonna turn this over to Dr. Saxton. He's gonna talk about psychopharmacology. Good morning, everyone. I definitely wanna echo John Renner's comments that it's great to see you all here. The enthusiasm for learning, and from the questions, obviously some of you are already doing this work and saving lives. But for those of you who may not be doing it yet, this is a great opportunity for psychiatrists to really make a difference in public health. So we're gonna talk about the pharmacology of methadone, buprenorphine, and naltrexone, the three medications that you already know about or have heard about. So starting with methadone, which of course cannot be prescribed right now, can only be ordered and dispensed in a licensed opioid treatment program. How many of you work in licensed opioid treatment programs? One or two. So other than that, the rest of you will likely not be using methadone, but you may encounter some patients on methadone for whom you're providing psychiatric care. So it's good to know about it. So this doesn't naturally occur in the opium poppy. It's a synthetic medication, has been known about for almost 100 years, and FDA approved for quite a while. And in the early 70s, that's when we really discovered that the treatment of opioid use disorder requires medications for successful outcomes. And for many years, people going to a licensed opioid treatment program to get methadone was really the only medication or adequate treatment available. Methadone is metabolized in the liver. It's very complex metabolism. There are many, many CYP450 enzymes involved, and there's a range of capacity to metabolize it. We have people who are ultra slow metabolizers, and they would be the people who end up with a long half-life. And then we have rapid metabolizers who may actually not be able to do well with once a day dosing and might need split dosing. That all has to be determined clinically because we don't have any biomarker to tell us how people metabolize it. There is a inactive metabolite, EDDP, and I can't even attempt to say the actual chemical name for it, but we all know it by that acronym. And that's what is often looked at in urine drug screens to determine whether methadone has been ingested or not. And you can see there's a range of oral bioavailability. So let's talk a little bit more about the pharmacology of methadone. So to orient you to the little graphic, the y-axis is looking at new opioid effects, and the x-axis is looking at increasing dose. So what you can see and make sense, if you look at the green line, which is a full agonist opioid, and that includes methadone, as you give more and more dose, you get more and more effect. And what happens to a human being when they get the maximal effects of new opioids on the new receptor? Okay, so we have a slightly, I thought we were a more active audience. You're slightly passive. It's early. You'll get some coffee on the break. But the full agonist new opioids suppress our respiratory drive. Our diaphragm, the phrenic nerve stops sending signals to the diaphragm. Our diaphragm stops going up and down. In other words, we go into respiratory arrest, and that would lead to an overdose. So that can happen with methadone, and that's one of the reasons why methadone, for now, we think this will change, and people like you who are experts could be able to prescribe methadone out of your offices, but that's five or 10 years down the line, most likely. So right now, it's a situation where people have to go to a program, ingest their medication under observation, and get a limited amount to take home, depending on how stable they are, to prevent an overdose on methadone. And we'll talk about these other lines in a moment. You see the line for buprenorphine, which is blue, and you see the red line for an antagonist, which is naltrexone. So we mentioned the half-life already. It depends on a person's capacity to metabolize methadone. Methadone has relatively weak affinity for the receptor, so it can be displaced by partial agonist, buprenorphine, or by full antagonist, like naloxone or naltrexone. And obviously, this is one of the ways that we can rescue people from an overdose. If they're overdosed on a full agonist, like methadone, or it could be morphine or fentanyl, we can give them naloxone and displace that full agonist from the receptor and get their diaphragm working again and potentially save them. And so we did talk about the respiratory suppression, and it is important to know that methadone can prolong the QTC interval, like so many other medications that we as psychiatrists use, and we need to be alert to that. And if there's clinical concern, check an ECG. And we know that if the QTC goes above 500 milliseconds, there's a higher risk for torsades de pointes, that life-threatening arrhythmia. Okay, we're gonna move to buprenorphine, which again is the bulk of what we're discussing today. So it's a, febane occurs naturally in the opium poppy, and with some minor chemical manipulation, that can be turned into buprenorphine. The metabolism is a little simpler than what is with methadone. It's primarily the 3A4 enzyme. And buprenorphine has an active metabolite, norebuprenorphine. So we suspect that norebuprenorphine is not quite as potent as buprenorphine, but it makes a little less difference whether people are metabolizing rapidly or slowly, because we're gonna still get a buildup of the active metabolite. And so, most is excreted in the gut, but some does appear in the urine, and that can help us if we're looking for buprenorphine adherence, because we can test for it in the urine. Now, buprenorphine is not going, I think everyone probably knows buprenorphine is not going to be effective if swallowed down in the gut, because very little is absorbed, and what is absorbed goes through first pass metabolism, turned into the active but less potent metabolite. So, the routes of administration that we're using clinically now are either going to be the sublingual route, where the tablets or film can be reasonably well absorbed, with, you see, bioavailability 30% or sometimes even greater, or we now have injectable forms that are going to have greater bioavailability. And I should say, there has been for a long time an inject, a short-acting injection form that was approved to treat acute pain that is very rarely used, but it is available, not to treat opioid use disorder. Okay, so we are back to our graphic here. And so, buprenorphine has a long half-life. That means it can be taken once a day, and there'll be enough medication, even when taken sublingually, in the system, generally, to suppress withdrawal. So, we often encourage people to take it once a day. Sometimes patients prefer to take it several times during the day, and that's really something they're going to decide, not something we're gonna struggle with them about, because once they go home with the medication, they're probably gonna take it the way they want to take it. And here is a really important point about buprenorphine, why it's so safe, and why we can prescribe a 30-day supply, even with refills, and send the patient out. And we don't have to worry, like we do with methadone, that someone might inadvertently or intentionally overdose. So you can see in the graphic that we're focusing on the blue line. In contrast to the full agonist opioid, if you give more and more and more with more dose, the first part of that curve parallels the full agonist opioid, correct? And then we get this plateau or ceiling effect. And we don't get any further, no matter how many receptors we saturate, we don't get any further opioid effect. And what that's doing is protecting against respiratory depression. Now, at higher doses, we see that blue curve paralleling the red curve, which is the antagonist. And so we can feel very, very confident in adults with buprenorphine alone, that even if they could take large enough dose to overdose, which is pretty hard if you're taking sublingual medication, they wouldn't have an actual lethal overdose. So that is one of the outstanding hallmarks of this medication, the safety factor that makes it very comfortable for us to prescribe. Now, some of the other important characteristics are that it has very high affinity for the receptor. So it's going to go to that new receptor, occupy it, exert some opioid effect, not as much as a full agonist. But while it's sitting on the receptor, the full agonist can't come along and get into that receptor. So a good metaphor for thinking about this is a lock and a key. If we think about the receptor as the lock, it's got a specific three-dimensional shape. When we have the right key, we can get that fitting right into the lock. And if we turn the tumblers, we can open the door wide. With buprenorphine, that's a full agonist. With buprenorphine, the key fits in the lock. It turns the tumblers, but we've got a safety chain on the door. The door can only open partway. No matter what else we do, that door's not going to open wider. So it's sitting on the receptors. It's preventing the full agonist from getting to the receptor. But the other point about a partial agonist, which is depicted on the graphic, again, by those pink arrows, if someone has full agonists in their system and we give them buprenorphine, it's going to kick that full agonist off the receptor. It's going to occupy the receptor. And since it exerts a little less opioid effect, what's it going to do? It's going to bring the opioid effect down and make them feel like they're in withdrawal. We call that, if it happens, precipitated withdrawal. The same thing can happen with an antagonist. So as you're going to hear later, we have to be thoughtful and clinically astute as we begin to start patients on this medication. Once we get through the initial starting of the medication, we don't have to worry about precipitated withdrawal. Once we get enough receptors occupied by buprenorphine. And it tends to, it's very sticky to the receptor. So once it gets on there, it doesn't come off easily. When we talk about medications or drugs binding the receptor, it's not a static situation. It's a situation where they're on the receptor, they come off, they go back on. And so buprenorphine tends to stick on there. And again, that's going to block other opioids from coming on. So we talked about the fact that it sticks to the receptor, what does it do? So once it's on the receptor, and once we've gotten enough receptors occupied, it's going to prevent withdrawal symptoms. And again, it should, ideally we're looking for zero withdrawal. Patients are going to feel more comfortable and do better in their functioning if they are not bothered by nagging withdrawal symptoms. It's also ideally going to decrease cravings, so that even if patients aren't having withdrawal, withdrawal can drive craving. But even without withdrawal, patients can begin to think about, oh, I remember when I used that heroin, or when I used that fentanyl, or I used that oxycodone, I felt pretty good. I want to feel good again. So even if they're not having withdrawal, that can happen. But if we get the buprenorphine dose adjusted properly, in most cases, we're not going to see a lot of craving, and we're trying to suppress that craving. And again, it's going to prevent an overdose with other opioids, because while it sits on the receptor, the other opioids cannot get in there. But it's not going to entirely block all the effects of most opioids. And so you already saw the data from Dr. Renner. It's common, especially early in treatment, for patients to test out other opioids and feel some effects. And particularly with fentanyl around now, which is so potent, we do hear the report from patients that even when we think they're on an optimized dose of buprenorphine, they might somewhat feel the effects of fentanyl. So what we don't want to do is get discouraged that, oh, this patient is still using some opioids, and treatment's failing. No, that is not the case. Treatment is working as long as we've got them coming back and getting their medication, and as long as they're not overdosing. Yes, we want to work with them over time to stop all their opioid use. But if it's occasional, and it was multiple times a day, the occasional is a big improvement over what was happening previously. So let's look at some of the data. The graphic here is from an older study from the 90s, one of the first ones that was done. And to interpret it, I just want to let you know that this used a different formulation of buprenorphine. It was sublingual, but it was an alcohol-based solution that has somewhat higher bioavailability than the tablets or film that we use now. So you have to think about the doses a little bit differently. So you can see by the colors, they put patients on doses from 1 milligram per day up to 16 milligrams per day in the red. And so when it says 16, that's probably more like if we gave 20 milligrams of the formulations we have now. But in any case, what we're looking at there is the buprenorphine dose on the x-axis, and the percent with. These are people just starting treatment, too, with 13 consecutive opioid-free urine specimens. In this study, they were giving urine specimens three times a week. So that's basically how many people for the first four weeks of treatment didn't use any opioids at all. And you can see, even in the first four weeks with 16 milligrams, that was up to 25%. And there is a clear dose response. So we know that we can prevent withdrawal on doses from 4 to 16 milligrams a day. Typically, sometimes we have to go higher. And we're going to be in the range of at least 8, typically, to up to 32 milligrams, which, at this point, is the maximum dose that's really been looked at and studied for opioid use disorder to get enough receptors occupied and prevent overdose. And we don't know for sure about how dose is related to keeping people on treatment. But there hasn't been a randomized controlled trial comparing a moderate dose to a higher dose. NIDA is trying to do such a study right now. We'll see how that works out. But the observational studies do suggest, in most cases, not every one, that higher doses are associated with. And again, we can't impute causation, but are associated with better retention. So in my opinion, we shouldn't be shy about optimizing the dose by going a little higher if necessary. And we'll talk very specifically later in the day about what you're going to be looking for. So every patient's different, just like anything else we do in psychiatry. And we're going to evaluate the patient clinically and optimize the dose based on the patient's response. This is that same study we just talked about, the dose ranging study. And what you can see is this sort of yellow line is the one milligram, which is an active placebo. We wouldn't expect one milligram would be sufficient to do much. And the people on only one milligram had higher levels of craving. So any active medication suppressed the craving. We do know that craving, obviously, as you'll hear about, is one of the DSM-5 criteria for diagnosing a use disorder. But some recent studies do suggest that craving is tied to outcomes. So patients who are being treated for a substance use disorder who have a lot of craving are likely to do less well than those who don't have the craving. And we have not perfect, but we have the tools in our toolkit, the right medication, to suppress craving to a fairly large extent. Now, the question has already come up, when do I take people off their medication? And I will tell you my bias. I think we should be asking somewhat the opposite question, which is, how do I keep my patients on their medication? Because we know that the first few weeks of going off medication is a very high risk time for overdose. And yes, there are going to be some patients that we've already talked about who want to get off buprenorphine. And I'm not going to, if my patient comes to me and says, I really want to get off, can you help me do that? I'm going to tell them the potential risks and potential benefits. If they want to do that, that's fine with me. I'll work with them. If they do get off, I'm going to follow them very, very closely. And we heard from the gentleman already that he had a couple of patients who relapsed. So I would rather even get them back on medication when they start having cravings before they relapse. Or, as we'll talk about with naltrexone, maybe get them on naltrexone. But what you see here in this study, patients were all stabilized on a dose of buprenorphine. And then that was either continued or they were put on a taper. And what we're looking at is how many were retained in treatment. What you can see so clearly is, so yes, when they were tapered, they weren't going to have medication, but they still were going to get behavioral interventions. What you can see so clearly is, as soon as the medication stops, people start leaving treatment because they just need medication to be able to function well. That's just an argument for keeping the medication going. There are some side effects. Although it says common, other than the constipation and dry mouth, the first two are actually very rare in people who have opioid tolerance. Headaches are maybe 10% to 20% of the people. In my experience, if they occur, they can be very easily controlled with NSAIDs or acetaminophen. And they tend to diminish over time. I've had a few patients who have these intolerable headaches, and that's probably just not going to be the medication for them. But that's a drop in the bucket compared to all the patients. I don't really see nausea as a common side effect. For an opioid-naive person, buprenorphine is very emetogenic. It really causes a lot of nausea. But for people who have opioid tolerance, we just don't see it very often. If they have it, you can slightly reduce the dose, or you can co-prescribe an anti-emetic. Constipation is pretty universal. You can see from the slide how to manage that. Usually good hydration, a little bit of exercise, diet. Sometimes we do need to prescribe stool softeners. It says naloxajaw, which is a form of naltrexone that doesn't get into the central nervous system, so it's only acting in the gut and would oppose the effects of buprenorphine. I've never had to prescribe that. The constipation just isn't that bad. Now, the FDA in the last couple of years did put a warning on sublingual buprenorphine about dental effects. And many of us have some doubt that the medication is actually causing that. We think that people who have had opioid use disorder have probably been neglecting their dental health. And we all know it's very frustrating as a psychiatrist that I can get health care coverage, usually for many of my patients, and take care of their major health issues, but they can't get dental coverage. And a lot of our patients, whether it's opioid use disorder or anything else, have dental problems. So we think it's more an issue of not the medication causing it, but other factors causing their dental problems. We don't really know for sure. But it can cause dry mouth, and you can take some action about that. I don't often hear that actual complaint from patients. Now, I talked to you about the respiratory suppression and how there's a plateau. And now I'm just showing you the data. So on the x-axis, we have doses from placebo running up to 32 milligrams of buprenorphine. On the y-axis, for the left panel, we're looking at respiratory rate. So you can see that the rate somewhat decreases as you're going from 2 to 4 milligrams. But then there's that plateau. So even when we get it to 32 milligrams, there's no more decrease in respiratory rate. And what we're seeing on the right panel is the O2 stats. And again, there's a little bit of a decrement, nothing clinically important. So even up at 32, there are 95%. But we just don't see that going into a range where we're going to have to worry about it. Now, if you're prescribing the sublingual formulations, you're mainly going to be using buprenorphine slash naloxone. Very important point, the naloxone is not there to have any treatment effect. It's there to prevent parenteral misuse. So you've heard about the bioavailability of buprenorphine when taken sublingually. Naloxone has extremely poor bioavailability from the sublingual route. Now, that does not mean it has zero. So some naloxone does get into the bloodstream. But not enough to precipitate withdrawal or really cause any problem with the buprenorphine dosage. And actually, it's interesting. They did a study comparing the bioavailability of buprenorphine slash naloxone with buprenorphine alone. And when the naloxone's in there, for some reason you don't understand, a little more buprenorphine gets absorbed. So even if there's some naloxone on the receptors blocking it, there's probably more buprenorphine there. And it really doesn't have an impact in the vast majority of patients. However, if someone should take the pill or the film and melt it down or crush it and try and inject it, you've got the naloxone competing with buprenorphine for the receptor. And they have about equal affinity for the receptor. So it's going to, and I'll show you the data in just a second, it's going to block the high effect. And so people are just not gonna be that motivated to inject the combination product. Not that they never do, but they're not gonna get much out of that, whereas buprenorphine alone can cause something of a high. And so that's why we recommend, in general, using the combination product rather than the buprenorphine alone. Now, I will say that there are a small number of patients who will come and tell you that they get side effects from that naloxone, or they might even say I'm allergic to naloxone. They are not allergic to naloxone, but they believe, rightly or wrongly, they're absorbing enough naloxone that it's causing them some side effects. I have some colleagues in Washington State who firmly believe what the patients are telling them. I don't know if it's expectancies or if it's a real effect. I don't think there's any way to tell that for sure. But it happens so seldom. If the patient says I want just the plain buprenorphine, that's really not a battle I wanna fight. I wanna make sure they're on buprenorphine even if it's not the combo product. And so I just will say, okay, I'll give you the monoproduct. Now, my colleagues may feel differently, or some of you may feel differently. I'm just giving you my opinion there. And I don't see that very often. So here are the data. This was an inpatient study. These were people who were accustomed to opioid use. And while they were inpatient, they actually were maintained on some morphine. And they had a number of studies done. And in this study, they got one of four injections. They either got, in the yellow, buprenorphine naloxone. And these are IV injections. Just plain naloxone, just plain buprenorphine in the blue, or a placebo in the turquoise, I guess that is. And so, and they're on the y-axis. So we're looking at time on the x-axis, on the y-axis. We're asking the patient to rate how intoxicated they are, zero to 100. So you can see with the dark blue line, that's buprenorphine alone. Very, very quickly, the patients are having a sense of intoxication. Now, it's not that much. It's 25 out of 100, but they're still feeling it. And then compare that with placebo or naloxone. They don't feel anything because those are not stimulating the mu receptor. The important comparison here is the yellow line, which is buprenorphine naloxone. And like I said, naloxone's competing for the receptor. So in the first two hours, there's very little effect of a high. And if people are injecting an opioid, they are looking for a quick response. They're not trying to take something that's gonna affect them a few hours later. So that's how well it works to prevent parenteral diversion. So I think we covered all of this, but yes, I agreed that the combo product is less likely to be diverted. Again, I will prescribe the monoproduct if that's what patients insist on. And could they be asking for that just because they wanna take it and sell it? That could be. I can't tell that for sure. I would rather have them in treatment than say I can't take that other medication on bleeding treatment. Your decision how you wanna manage that. How well does buprenorphine work? So there's been a big Cochrane view that compared buprenorphine to methadone and to placebo. And we're just presenting the conclusions here. So buprenorphine was effective for retaining patients in treatment above two milligrams and suppressing illicit opioid use at higher doses. I should say, take this into consideration that all of these studies were done the pre the fentanyl era. So we don't have these kinds of data for the fentanyl era. And in this Cochrane view, the medications were given at adequate doses where methadone and buprenorphine were pretty comparable at keeping patients in treatment. And when we got up to higher doses, more than 16 milligrams per day compared to over 85 of methadone. Again, they worked pretty well to suppress heroin use and work equivalently. I will tell you just this week, a new meta-analysis came out that included, I think it doesn't say, yes, that's 2014, so almost 10 years ago, the study reporting here was done. The newer one came out that includes studies done since then. And they did conclude that methadone may have a slight edge in retention and that buprenorphine might have a slight edge in suppressing illicit opioid use. Again, all that work was almost all done pre-fentanyl, so we don't know for sure. But I think the bottom line here is you can feel very confident that buprenorphine is the top line treatment for opioid use disorder. And yeah, there may be some people who fail that and need to go to methadone, just like when we're treating depression, patients may not respond to their first antidepressant and we make some medication adjustments. Sometimes we need to do that with opioid use disorder, but buprenorphine is a great starting place. A large number of patients, probably 30% or more who have opioid use disorder, also use benzodiazepines, some by prescription, many buy them illicitly, which in the present day is very scary because what is sold as alprazolam on the street sometimes now is containing fentanyl. So we don't really know what they're getting, but the use is very common. And of course, we showed you that buprenorphine alone is not gonna stop an adult from breathing, but it's possible a combination of benzodiazepines and buprenorphine could come closer to that. And there have been some reported cases of fatal poisonings usually when the benzodiazepine is injected, which happens in Europe, but not too often here. So prior to 2017, there was a boxed warning saying, don't combine opioid medications with benzodiazepines or other sedatives because of the risk this combination could cause an overdose. They changed that six years ago because what they saw is people like us were getting scared and saying, well, this patient is misusing benzodiazepines, so I can't treat that patient with buprenorphine. And then the patients are going out and using illicit opioids and dying of overdoses. So now the new guidance is, yes, we wanna monitor these patients very carefully, but we don't wanna withhold buprenorphine because someone's on benzodiazepines. And that's a question I get very commonly is less experienced clinicians are worried, am I doing something wrong if this patient is either prescribed benzodiazepines or misusing benzodiazepines and I prescribed buprenorphine and no, you are not doing something wrong. It's not ideal, but the lesser of two evils is to continue the buprenorphine and work on the benzodiazepines over time. So if you're gonna have patients who are buprenorphine or methadone and using other CNS depressants, sometimes they're being prescribed for an inaccurate diagnosis, and at least you can determine do they really even clinically need a benzodiazepine. That doesn't necessarily mean it's gonna be easy to get them off of it when they started. I mean, how many of you prescribe benzodiazepines to your patients? How many of you, once they're on benzodiazepines, so psychiatrists will use them often, how many of you can get your patients off benzodiazepines easily? Okay, well, you're gonna have to tell us the secret back there. I sure haven't had very good luck with it. Some patients I have been able to taper, oh, she's gonna tell us, okay. Well, I don't say that it's easy all the time. Bend the mic down, see. I don't say that it's easy all the time, but most of the time, if you start off the benzodiazepine by telling them that, you are gonna taper so that they know what to expect. And if I have a patient who comes in with benzodiazepines on board, we agree to a very slow taper. Somebody who is on, I had somebody on six milligrams of Klonopin a day. And it took me around about two years to get them off Klonopin. So I mean, I don't slash and burn. We take time. But it's not easy, I'm not saying that. Okay, so, yes, I think that we all would agree that a slow taper is what's the way to go. In my experience, 10 to 20% succeed in getting off, and most of them, when the dose gets lower, they start to get symptomatic, and they don't want to get off of it. So it's worth trying that. But again, if you can't get them off of the benzodiazepines, don't stop the buprenorphine. Keep the buprenorphine up, keep working on the benzodiazepines. Similar issues with alcohol. So about 25% of patients with opioid use disorder also have alcohol use disorder, so you're gonna see this commonly. Maybe buprenorphine helps a little bit with the alcohol. I wouldn't say that it's impressive. And so we have to think about treating the alcohol use disorder, which is actually probably easier in some ways to deal with than the benzodiazepines, because we have a little better success at getting people off of alcohol. So if they have alcohol withdrawal symptoms, we probably either need to do an out, I gotta get going, okay. We either need to do an outpatient taper, or in some cases, if they have a history of DTs or seizures, we might want to admit them to withdraw them from alcohol. And then we can think about using behavioral interventions or medications for alcohol use disorder. The most commonly used medication for alcohol use disorder is naltrexone, but we cannot use that with our patients on buprenorphine because it's an opioid antagonist. So we'd be looking at the other medications, like acamprosate, disulfiram, gabapentin, topiramate. A couple of those last two were off-label. Okay, we're gonna very quickly talk about naltrexone. I am not sure if I missed the slide. It doesn't matter because I gotta hurry up anyway. So if we block, if we can succeed in getting a patient on naltrexone, we're blocking the mu receptor, and that patient tries to use opioids, they're gonna get zero reinforcement. Because this is really effective at blocking the receptor. It just totally eliminates the possibility of, unless the doses are massive, of any opioid getting in there. So they try it a few times, they go, I'm not getting any effect from this, so I'm gonna stop doing it. But also, it's important to realize, in animal studies, opioids cause the release of dopamine, which is the main neurotransmitter, mediating reinforcement and reward. And in animal studies, what we see is the release of dopamine occurs before the drug is taken, but in anticipation of getting the drug. So people who know they can get an effect they're looking for from a substance, right before they take it, they're already getting reinforcement from the expectation. So if we can block the mu receptors, and the opioids are not causing that dopamine release pre-drug use, we can also decrease the cravings and the desire to use the drug. So this was a study done in Russia, and all of these patients were admitted for a month, and completely tapered off their opioids, and then they were randomly assigned to long-acting injection of naltrexone, which lasts for 30 days, or to a placebo injection. So the very left, we're looking at how many patients remain opioid-free, with the red being an active medication, beating the placebo. The middle panel, we're looking at craving, with the red, much decrease in craving. And on the right panel, we're looking at retention and treatment, with red superior to the placebo. So that's how well it works, once we get people on it. The graphic you see here, the yellow is comparing oral naltrexone, which you get daily peaks and valleys, to the long-acting injection, where you get a peak in the first couple days, and then you get a gradual tail-off, where you've got a constant plasma level, above what we think we need for a therapeutic effect. And we do find, this study compared the oral naltrexone to injectable naltrexone, and found that people were better retained in treatment with injection, so that's what we certainly find to use oral, for selected patients who are highly motivated, but in general, we recommend the injection. Here's the hurdle, getting them on naltrexone, they have to be opioid-free, in general, for seven to 10 days. That's a very hard hurdle for most patients, who have bad withdrawal and a lot of craving to overcome. So one of the audience members said earlier, not many people want the naltrexone, and that's probably true, but there are some selected patients who want it, and particularly if you have access to an inpatient unit, where they can do their seven to 10 days in a controlled environment, that may work for people. We do see some people who are really motivated to take naltrexone, you could help them through the withdrawal using medications like clonidine, which we'll talk more about later, and there are some more rapid methods. So we have the withdrawal treatment, and here, and the naltrexone beginning, so sort of three basic methods. We can start them on buprenorphine and taper that, and they still need seven to 10 days after the last buprenorphine. That's the upper one. We can use clonidine and other comfort medications, and so starting from day zero, seven days later, they can maybe start the naltrexone, but the, we'll go over this slide again, but the bottom one actually uses, starts naltrexone early at very low doses that would require a compounding pharmacy. So it's not very practical for regular clinical use. So this study compared buprenorphine to injectable naltrexone in patients who started out in a residential or inpatient setting where they were being withdrawn from their opioids, which were mainly heroin or prescription opioids, and so because it was harder to get on naltrexone, the left panel, A, is the intention to treat analysis, and what we're looking at is how many relapsed over time, and the red line is the injectable naltrexone, compared to the blue line, buprenorphine. You can see that buprenorphine beats the naltrexone in the intention to treat analysis. That's including everyone who was randomized to one condition or the other. The B panel is the PER protocol, so it's only including the naltrexone people and the buprenorphine people who actually got on medication. So once they're on the naltrexone, it looks very equivalent to the buprenorphine in terms of preventing relapse, but it's just harder to get them on. Okay, so I think that I'm not gonna do the summary because I'm already over time, so do you want me to do the summary? Okay, so we can use methadone, buprenorphine, or naltrexone. With any one of these forms of treatment, we keep people engaged in treatment better than we would without medication. So it's really not even, unless patients refuse medication entirely, it's not really ethical in 2023 to be treating opioid use disorder without medications. We don't want to get people off quickly unless they insist. We want to counsel them to stay on medication, maybe as a lifelong intervention. And we have to be cautious with buprenorphine and methadone when people are on sedative hypnotics, but it's not a contraindication. Okay, so we have some polling questions. I'm not sure how to work the polling questions. Okay, okay. The affinity of buprenorphine results in, A, a strong bond to the mu opioid receptor, B, displacement of buprenorphine by methadone, C, a prolonged bond to the mu opioid receptor, D, an enhanced euphoric effect of buprenorphine. So let's see what people think. Ah, okay. A strong bond to the mu opioid receptor, a prolonged bond to the mu opioid receptor. I think both of those are sort of correct, so trick question, so let's see. Well, everyone got it right, so we must be doing a great job with this course. Okay, now we're gonna have DC come up and talk about evaluation. Hi, nice seeing you, everyone. Just a quick question. How many of you have patients on buprenorphine right now, currently? Great, and thank you. So just kind of like a shout out, if you guys actually want to learn more about buprenorphine, there's a free workshop at 1.30 tomorrow. There's a Buprenorphine Course 201 update. You don't have to register for it. You don't have to pay for it. So if you have more questions about buprenorphine after going through today, you can come to tomorrow's workshop. I know it's been a long morning. We're gonna just power through this until the this portion and a case presentation by Dr. Lebronis, and then we'll take a break afterwards. I'm not gonna take questions until we are done with the case one, but I'm sure throughout the course of the day, we're gonna have time for more discussion and the questions and answers, okay? So I'm gonna be talking about the evaluation piece, and I'm not gonna tell you that it's a thorough HMP taking before starting buprenorphine. I mean, you guys already know that. One point that I do want to make is that, sure, it'd be nice to have a comprehensive history and physical, including their psychiatric and medical, and substance use disorders, but please do not let that delay their treatment. For example, I think, especially if you're deemed as an addiction specialist by your institution, you'll be sometimes asked to see a patient who just was meeting with their PCP or who had just walked in for their sick visits, and then they disclose that they've been struggling with the oxycodone or fentanyl. Then, if I get called in to see those patients, then what I do is I'll do composite, just brief history-taking for 30 minutes, and that'll be enough for me to determine that I should talk to them about different alternatives, but this patient needs buprenorphine, then I'm gonna start it. I'm gonna try to aim to start that as soon as possible. We're gonna talk about what you should probably do throughout this session, but that's the main point. Building a therapeutic alliance, that's probably the biggest counseling piece. A lot of patients who are coming into treatment for buprenorphine, they already have, they have already experienced the stigma from the society, from the medical providers. They're already ashamed about it. They may be already told by other clinic, we cannot give you buprenorphine because you're not stable enough, or you're not good enough, or whatever the reason may be, and they already have a stigma about their struggles already. They're very much ashamed. They're not sure if they're gonna be judged by me. They're not sure if this is gonna be just in line with the, they'll be already projecting that I'll be judgmental towards them, so building a therapeutic alliance is probably the biggest piece, and just normalizing their experience, normalizing the opioid epidemic, and normalizing their struggle with their underlying psychiatric issues, or pain, or substance use disorder itself, and so attitude-wise, and just remain respectful. I mean, the horror stories that my patients share that they come into, when they walk into the ED, and they disclose that they've been struggling with the opioids, or the fact that they're on suboxone, or buprenorphine, and they tell me that the attitude of the ED providers, or other frontline providers, changed like this. My patient walked into the ED, talking that they're worried about having a kidney stone, and the moment he disclosed that he was on buprenorphine, the provider, the ED provider, told him, you know we don't provide opioids, right, from our ED, and the patient was like, I'm just here for my flank pain. Just valuing and keeping in mind of their experience without a provider's, you know, would be helpful to kind of set the tone. You talk about honesty, dishonesty, or the tendency to lie, is that, you know, I don't hold that against them. If they tend to lie, or minimize it, that's a symptom of their substance use disorders, and it goes both ways. I try to be honest with them, I am honest with them as much as possible. I can talk, I can provide them, I can counsel them about the course of buprenorphine treatment, what they would look like, what my goal is for them, and what I would, you know, expect from them. Shared goals, why is the patient seeking treatment? Most often, patients have struggled with a substance use disorder for a long time. So why today, why did they come in today? Is that, you know, and it doesn't matter if their motivation is external, you know, if they're court mandated to be here, or if the family, you know, forced them to be here, or if they're, you know, they have an internal motivation, because a lot of times, patients will have both, components of both, you know? And then, just kind of like a, trying to get that, get them to verbalize their own goals to seek treatment, and, you know, use that as a, kind of like a tool to engage in motivational interviewing. So, you know, we'll be talking more about motivational interviewing later in the morning. And then, once you identify their goals for treatment, and what they want to do, then you can kind of tell them, that, you know, so if, you know, for example, if their goal was to be on Suboxone, buprenorphine, sorry, every weekend, you know, when they're not using heroin, and if the goal was too far from what we provide, and what we want to see, then you want to sit down with them and counsel them about the pharmacology of buprenorphine, and how that might not be compatible with their own goals. But here's what we can do to help you. Reassurance, so confidentiality. So, obviously, you cannot be, you cannot keep their medical history confidential from their insurance companies. You cannot provide their medical information confidential from other healthcare providers. So you can be, you know, you can assure them, look, unless, you know, there's added protection for history with the substance use disorders for religion information. And then, when you do sign religion information, we're gonna ask for your permission, and we're gonna ask, actually, to check off an extra mark, so that, you know, it's okay, from your perspective, for us to disclose your healthcare information related to substance use disorders. So, having said that, I, you know, encourage them to consider involving their family members in their treatment plans. It's, if they can, if I can get their parents, or spouses, or children, or partners into the treatment plan and just kind of, like, have their, you know, shared goals and management, it tends to work out better. Thank you. As Dr. Reiner said, addiction is one of the most stigmatized conditions. Individuals with substance use disorders are viewed more negatively than people with physical or psychiatric disabilities. I've, you know, you've probably heard about junkies, or opiate users, or heroin users. They're often viewed as, you know, has a weak willpower, or, you know, they were selfish, or they have antisocial personality disorder. They chose to spend their money on their pleasure instead of their, you know, taking care of their rent, or, you know, buying the diapers for their children, or taking care of their spouses. And the, just being committed to use the recovery language is very crucial. Every little thing matters. You know, I, you know, recently kind of, you know, got into with our pharmacy department, because the pharmacy had a, you know, our pharmacy had a drop-down menu for buprenorphine prescription, and said, this is for narcotic addiction. I said, actually, that's an archaic language, and we can, if you can put, change that to opiate use disorder, that'd be a lot better. I still, you know, catch myself using the terms like clean urine, dirty urine. Oh, you know, his urine test was clean from last week, or his urine test was dirty from last week. That, you know, sometimes you can use, it was an expected result, or it was, you know, it was free from illicit substances, and try to keep in mind of that. Goals of evaluation. So, first of all, I told you, it is to set the alliance. It is set to therapeutic alliance. I'm here for you. I'm here for your recovery. I'm here to help your goals. And like I said, use the language of recovery and show goal settings. I think for most states, I believe, if not all, require prescription monitoring programs before prescribing buprenorphine. Buprenorphine, as you know, is Schedule III. For Massachusetts, it certainly requires checking the state PDMP. And if you can, try to get quality information from your significant other. And if they absolutely refuse, then so be it. I'm not going to push for that. I'm not going to let that prevent me from treating them with a buprenorphine, but it'd be nice to have. Try to get the quality information from other treatment providers. But I'm not going to delay their treatment with a buprenorphine unless, like until I get that information. If I determine that this patient is clearly struggling with an opioid use disorder, he's in withdrawal, or he may not be in withdrawal, but he's struggling with the cravings right now, then I'm going to start the treatment right away. Comprehensive assessment. Like I said, it'd be nice to have met with them for two hours, having done comprehensive psychiatric evaluation, and having them go through physical, and get all the labs necessary, and test for HIV, and Hep C, and all the other things, and get the quality information from the significant other and treatment providers. That can be done maybe a week later or a month later. The most important thing is to get the timely treatment. We'll be talking about this later on, but there's emerging evidence that the buprenorphine treatment from the ED is very, very effective. So think about your experience through the ED. ED doesn't have all the time in the world. Sometimes you're like, oh, if I don't treat them right away, they may never come back. I need to treat them while I got them here. And they got the luxury of having the fast lab turnout, the stat lab, and being able to do medical assessment right then and there. But they'll be actually starting buprenorphine from then and there. And they have seen very promising results. Signs of withdrawal. If there are signs of withdrawal, so Dr. Wenner will talk more about how the withdrawal symptoms come into play when you first time the buprenorphine dose. The clinical opioid withdrawal scale will give you objective measures of how much withdrawal they are in. Diagnosis and clarification of substance use disorder, DSM criteria. So I have the luxury of working in the substance use disorder program. I call it a luxury, because I feel for my colleagues and friends in the front line. Because I have the luxury of seeing patients who have already decided to come see me. So they have opioid use disorder. I'm not there to try to convince them, trying to provide intervention if they have problems with the opioids. I don't need to go through the wall of text of DSM-5 criteria to see if they have opioid use disorder. By selection bias, by the time they come see me, they have opioid use disorder, most of them. And if you have the time for it, you can go through to use that as a tool to convince them to get treatment for DSM-5 criteria, whether it be mild or moderate or severe. Assessment for appropriateness of buprenorphine treatment, any contraindication. I will say that the methadone, for example, by law will require for the patient to have at least one year of opioid use disorder history. Buprenorphine doesn't have that kind of requirement. I have a pretty low threshold to determine that they are deemed appropriate for buprenorphine. If their opioid use disorder is less than six months, if they tend to be on the younger side, I counsel them about whether buprenorphine is the right treatment for them. If their opioid use disorder, like a dependence, if the physiological dependence has been less than six months. Because when I counsel them about the buprenorphine treatment period, I often talk about six months, six months plus, and then for an indefinite period of time. As Dr. Saxon said, I talk to them about how to keep them in buprenorphine treatment and how to make it convenient for them. But if a patient comes in and not having used opioids for more than six months, I counsel them. If you think buprenorphine is a bit of a treatment, if there's any way for me to offer long-injecting naltrexone. But if they say, no, I've tried this, I've tried that, from your counseling, buprenorphine is the right treatment. Then by all means, I go ahead with the buprenorphine treatment. So established diagnosis of opioid use disorder. Again, if you're working the front line and you're not yet sure if they have opioid use disorder. I mean, if you follow the DSM-5 criteria, physiologically, most often they'll already have tolerance and individual symptoms when they stop. And as long as you meet two of the nine criteria, then you can diagnose them with opioid use disorder. Obtain urine toxicology screen. We'll be talking about drug screens later on. So I'll be talking more about that in detail. So the urine screen is still the gold standard because of the optimal detection window time. Review prescription monitoring program. Hopefully, your EMR will be letting you check the state PDMP very conveniently. If not, you can inquire about them instead of you logging on to state PDMP every time you do it yourself. Signed forms, consent for treatment, consider multiple release. And the PCSS website has the helpful forms for you to use. Overall goals, identify individuals at higher risk. Patients with a polysubstance use, if they have comorbid benzoyl use disorder. Benzoyl, as Dr. Saxon talked about, sometimes often probably is the most biggest concern for me when I'm considering comorbid substance use disorders. Talk about the cocaine, whether they're using IV form or smokeable forms or snorting. If they have a complicated physical or behavioral health illness, if they have an unstable bipolar disorder or schizophrenia, that's obviously something that you have to keep in mind and start to target right away. And we're going to also be talking about social determinants of a patient's health later on. Develop a recommendation for treatment. I'm going to go through that. You can use some of the forms. In my program, we tend to use the BAM, or it's the Behavioral Addiction Monitor. That's the scale that we use. But you can obviously use the PHQ-9 to screen for, obviously, depression, audit to screen for alcohol use disorder, and the DASD-10 form. Medical history, again, I'm talking to a group of seasoned health care professionals. The only thing is, if your patient is a woman of childbearing age, please clarify pregnancy status. It is very easy to add the urine pregnancy test. And according to WHO, the only group of patients who are recommended for buprenorphine-only products are pregnant patients. So naloxone is still in category C. We don't know whether it'd be harmful or beneficial to the fetus or the pregnancy. We do know that the naloxone causes the placenta. So the buprenorphine-only products are recommended for pregnant patients. Having said that, I've talked with my colleagues in Boston Medical Center. They have the Project Respect, which has the specialized program for Dr. Lebonis. You should come. Yeah, hi. So yeah, yeah, OK. So I've talked with my class at Boston Medical Center. They specialize in taking care of pregnant patients with the opioid use disorder. They told me they've now almost exclusively using buprenorphine naloxone products, because they've seen better treatment outcomes with the combined products. And they have not seen any harmful effects from giving them combined products. So that's the anecdotal experience from Boston Medical Center. Dental care, we talked about this. Medications, as opposed to methadone, buprenorphine has less medical interactions. But you obviously want to get the combined list of their presence in the past medications. I'd like to get EKG, but I'm not going to wait for EKG before I start. So unless they're on a lot of QT supplementation, we have symptoms, substance use, prior diagnosis, trauma history, obviously very important, treatment response, inpatient detox, residential programs, past success, IOP, partial hospital. And I think I can safely just get past them. Social history, addressing their barriers to care is obviously very important. Addressing their insurance status, addressing their logistics, how they're going to get the treatment. If I'm going to ask them to come back in a week, can they have a transplantation to come in? Can I subsidize some of that with the telehealth visits? Family history, you pay particular attention to substance use disorders. And obviously, you're going to get the family history of other mental health and suicide attempts and other attempted suicide history. Substance use history, I focus my history, if I'm doing a brief composite history taking, on the opioids and benzos. But eventually, you want to get to know about what they have used and what they are currently engaging in abusing. Ask about alcohol, cannabis. Ask about the cigarettes. Ask about the set of hypnotics. And yeah. Age of first use, I think there has been some evidence earlier that they started using substances. Any substance is actually a prognostic factor. Obviously, the earlier they use, the prognosis is going to be a little slightly worse. Parents have used, especially if they're using IV, you want to make sure that they are not having any infection. They're utilizing safe injection techniques. Hopefully, they'll be utilizing the sterile program, the sterile kits to use the IV. The goal is to eventually for them to stop using IV. If they're telling you that they're using IV substance, then you want to counsel them about that. Assess the recent use. If they are still not in withdrawal from the most recent fentanyl use, then that will be in consideration for when you are timing the first buprenorphine dose. Again, more to come. Cravings and control. You asked about the cravings. This is obviously going to be in line with your counseling. In line with the CBT for substance use disorder, you want to think about if there's any room for intervention if they analyze the chain of their behaviors and thoughts when they have cravings, when they have more cravings, and others. This is also, you talk about their previous relapses and attempts to abstain. And yeah. I think we'll talk more about this if you have questions about this. I think this is pretty much basic. You think about their tolerance, about how much and how often they have to use more to get the same effects. That will also determine how severe withdrawal is going to be. And that can kind of guide you about whether you want to do in-office initiation of buprenorphine, or they can do take-home dose of buprenorphine to initiate buprenorphine. And the consequences of use, whether it be legal, family, professional, and social consequences. Physical exam. I think most often, some of the physical exams will be covered by obtaining clinical withdrawal scales. And they'll assess for any signs and symptoms of withdrawal. And obviously, you want to look for, especially if they have a history of IV substance use, then you want to look for any signs and symptoms of systematic or serious infection. Again, this is pretty much covered by the clinical withdrawal scale if you're assessing for withdrawal symptoms. If you're assessing someone with the ultramental status, you're kind of concerned for acute intoxication, then you want to actually check their pupil size. That's probably going to be the most telling sign, whether they have an opioid contributing to their ultramental status. Because a lot of other stethoscopes can make them look like opioid intoxication, but they cannot make the pupils constrict. Pregnancy test for women of childbearing age. CBC and platelet counts. Again, urine drug screening. You want to include buprenorphine and fentanyl. Buprenorphine and fentanyl will not be caught on opioid screening immunoassay. We'll be talking about drug testing more in the afternoon. Stem electrolytes, HIV testing. Obviously, you want to check for Hep C and Hep B. Get liver enzymes. So, Dr. Wu, I think I can defer this to the later on. Okay, yeah, the point-of-care testing. There's an immunoassay available for most commonly abused substances. We'll be talking more about the urine drug testing later in the afternoon. Screening is for immunoassay. Confirmation, when you talk about confirmation, it's talking about the gas chromatography, mass spectrometer testing. It is more expensive. It's a lot more accurate, but it takes time. The results are not going to be available in the same day. It's mostly going to be send-out test for your institution. We can give you a quantitative, and you reserve. I don't do confirmatory testing or GC-MS testing for every patient on every occasion, but if I have something that I'm concerned about, or whether this is going to make a significant change to my management of the patient, then I send for confirmation. Adjunctive testing of pregnancy, fentanyl. DSM-5 criteria. This PowerPoint is available to you. You can read it later on. It's also in the DSM-5 book, so I'll skip it. So whether you feel comfortable taking care of your patients in your program depends on how much resource you have. If you're a single provider doing a private practice and taking care of patients on buprenorphine, your, obviously, scope of practice is going to be limited compared to a university program that has a robust OBAP program. They have nurse care majors, and they have the support of the CBT-trained psychologist. And you can send them for frequent urine drug testing as often as you like. You can dose them every day. So your scope of practice will depend on how much resource you have. So you want to think about that. This is not something that I can handle. You want to think about looking into and referring them to a bigger and more robust program. You can still start them on buprenorphine and then talk about referrals later on. So I cannot tell you to start buprenorphine on every single patient from the sickly patient that you've seen in a single provider office, but it's not out of the line for you to start buprenorphine for those patients and think about and counsel about referrals to a bigger program as you can start the treatment. General principle, you want to avoid continued drug and alcohol misuse. So we'll be talking about the initiation of buprenorphine later on. One thing that I will counsel them, buprenorphine by itself, no matter how much they take, it's probably not going to kill a full-size adult. Not the case for children or their pets. It is their responsibility to keep their medication safely. We've had case reports of a toddler coming to buprenorphine, their parents' buprenorphine accidentally and they suffer significant injuries. So you want to make sure that your buprenorphine is stored safely and you want to counsel them. We'll be talking about the, so your eventual goal is to get them reduced or abstain from all substances and live happily ever after. It may occur when you first start buprenorphine as they reduce the opioid use, it may occur that they also are going to reduce cocaine or other substances. So it is not meant for that, but when that happens, I can never recommend them. If they continue to engage in other substance use programs, then you want to counsel them, but there are some more intensive care options. There's a residential care, there are options for partial hospital. I love partial, so I'm kind of biased. My program has a partial in IOP. And then the innovation, one of the innovations includes tele-psychiatry and we're doing a tele-IOP in our program and that's been working out very, very well. Treatment agreement, you just kind of, I know a lot of providers have this fear about, once I get them started on buprenorphine, they'll be demanding and they'll be entitled and then they'll be coming to get buprenorphine and it's going to open the flood gate and I'm going to be known as the provider who's giving out buprenorphine. That has really not been the experience or case for everyone that I actually talked to. But you do want to set the expectation from the get-go. You want to tell them, look, we want to see you're on drug screen. You cannot just no-show your appointments for six months in a row and expect to continue to get your buprenorphine. That's not how this works. And if you're, I'm going to be checking state PDMP if you're obtaining benzos from other providers without talking to me about it, then I have to think about the safety of the medications. I have to think about your overall health. So just making the expectations clear just from the get-go kind of keeps the patients happy and content. They may not agree with you, but they at least know what is expected of them. Examples of agreement can be found on tip 40 and 63. Again, the link is there. You can check them out. Summary, I'm just going to summarize. The most important thing is that you are here to help them and to convince them you're here to help them. They're already projecting their own fears about their treatment when they come in to treatment with you. And you're going to be doing your due diligence as a healthcare provider. You're going to be talking about psychiatric illness, psychiatric comorbidities, and other comorbid substance use disorders. But the biggest thing is to keep the language respectful and convince them that you are here to help them and that we can work towards their goals together. Polling. In taking a patient history, the clinician should maintain a confrontational stance to get honest answers. Assure patient that the objective is concerned for their health and is discussed confidentially. Not ask about the drug use as it will only create problems. Or should always have a release to talk to family members or support network before starting OUD. 100%, 100%, thank you. Point five, mild to severe opioid use disorder is different from simple physical use disorder because there is tolerance, or there are original symptoms on discontention of the drug, or there's compulsive use in the face of a variety of problems, or pain is the primary drive to continued use of the drug. Actually, this is something that I kind of skipped when I talked about DSM-5 criteria for opioid disorder. But let's see what the answer is going to be. Okay. Great, so just by the virtue of being on chronic opioid therapy, there will be tolerance, and there will be withdrawal. And there have been efforts to describe that these patients really should be separated from opioid use disorder. Some have coined the term persistent, complex opioid dependence. That has not really caught on. But when you're really evaluating for opioid use disorder, we're looking at the compulsive use despite problems in their professional, family, or social responsibilities. And that is the, oh, there's another question. So we're gonna actually get through this very quickly. When obtaining a substance use history in the evaluation of a patient for buprenorphine treatment, once you remember, buprenorphine is also effective in treating alcohol and other drug use. Patients with opioid disorder rarely misuse other drugs. Individuals using multiple substances may require more intensive treatment. If a patient is taking benzodiazepine, they cannot be prescribed buprenorphine. So I'll give you 15 seconds. Yes, individuals using multiple substances may require more intensive treatment. So thank you, and here's Dr. Lovonis. Thank you. All right, good morning, everyone. And thank you so much to my colleagues who invited me to come here and be part of this course. This is a highlight for my annual meeting at the APA, the buprenorphine course, and I couldn't possibly miss that opportunity to have some contribution to it by going through this lawyer case. Before starting, I just want to say that I came from another meeting and I heard something that I've never heard before that completely blew my mind as an addiction psychiatrist. I thought I've heard it all, but this really stuck to me. I found out that when it comes to gambling and gambling disorder in California, you can do a self-exclusion clause, which started in Michigan and goes to a lot of states where you declare yourself as a gambler and you self-exclude yourself and you're not allowed to go to casinos. But in California, you're allowed to go to the casino to lose money, but you're not allowed to go to the casino to win money. If you go into the casino and you win, they're gonna take your money, but you're fully allowed to just go in and lose as much as you want. I mean, how shrewd is that? It really blew my mind, the level of shrewdness of it. And I just found out that this morning. You can't make these things up. And in some ways, I thought it was an analogy for our patients, you're allowed to lose, but you're not allowed to win. It's just, it's really incredible to me. All right, back to buprenorphine and this wonderful course we're doing today. Let's just do a case. So, Mr. Smith is a 40-year-old man who comes to your office asking to be treated with buprenorphine. He is a criminal defense attorney in private practice and he knows about buprenorphine because you're treating some of his clients. His goal is to use buprenorphine during the week and occasionally use heroin by snorting on the weekend. He has used heroin for the past five years, okay? So, we do have our setting pretty well explained. However, for the past six months, he has used heroin primarily on the weekend, but he's concerned now because he has begun to use small amounts of heroin daily. If he doesn't use heroin, he gets loose stools, is irritable, and has difficulty getting and staying asleep. He has no desire to completely stop heroin use, but he doesn't want to use it during the week. His passion is playing jazz and he has organized a band. He says that heroin use is common in the club where his band plays. All the members of the band use heroin and many of his friends who come to the club also snort or inject heroin. He rarely buys heroin as his friends usually give it to him. Okay. His only other drug use is marijuana and alcohol, three to six drinks per night. Again, primarily used on the weekend. He has never been arrested or had significant medical consequences from his heroin use. He's not married. He has a 14-year-old son who has supported and sees often. Okay? We're pretty set with the case. Any clarifying questions? All right, let's just go to the questions that we have. Oh, there's a polling question. Okay, all right. So I guess there are two questions here. One question is what is the diagnosis? So let's just poll that one, the advanced one. No, I don't advance one. Happens automatically or? No. Oh, it's not a built-in thing. Okay, all right. All right, so what is the diagnosis? If somebody can shout it out. And I'll repeat it because we're recording the course today. Yes? It's a multiple drug use. What is it? It's a multiple drug use. Multiple drug use. Just to be clear here, we used to have a polysubstance use disorder or polysubstance dependence in earlier DSMs. Ever since, I believe, DSM-IV, we have moved to just individually listing each disorder. We don't have polysubstance dependence or polysubstance abuse or any of this, which of course keeps on showing up in a lot of charts in a lot of hospitals. The main reason for that is to encourage people to treat all these different individual disorders, perhaps most significantly tobacco use disorder that used to be lost in this polysubstance dependence that we used to have in the past. So individual drugs, what would be a diagnosis that we have here? Opioid use disorder. Okay, let's just go through the criteria. I know that you're gonna be studying them by yourselves later, but the way to remember, there are 11 criteria in the DSM-V. Think of them in three different buckets. We have the physiological component, tolerance and withdrawal. These are two of the criteria, the physiological part of addiction. Then we have the internal preoccupation. This is where people live with a drug at all times. They spend tremendous amounts of time obtaining the drug, using the drug, coming down from the drug. They have cravings for the drug. They have a sense of not being able to think about anything else but the drug. This is the internal preoccupation part, the second bucket. And the third one is external consequences. This is when you have medical consequences, when you have interpersonal consequences like your relationships go south, when you stop your hobbies, when your professional work gets affected and so on. All right, so these are the three major buckets of the DSM-V diagnosis. There is an uber criterion, in my mind at least, and that is continued use despite knowledge of adverse consequences. I know it's bad for me, but I cannot stop it. And at least in my mind, phenomenologically speaking, is the hallmark of addiction. Continued use despite knowledge of adverse consequences. All right, so think about that as the major DSM diagnosis for any addiction, including, of course, opioid use disorder. All right, would you prescribe buprenorphine to this patient? Anyone? Yes, all right, give me a little more of a reason why yes. And I'll repeat it because, again, we're recording the show. So it is difficult for him to continue what he's doing, so buprenorphine would help him stabilize his life and meet his goals, which is to not use, at least during the weekend. Will he be able to continue using, not use during the week, I'm sorry, that's his goal is not to use during the week. If he gets on buprenorphine, if he is prescribed buprenorphine, will he be able to use heroin over the weekend? No. The official line would be no because his receptors would be blocked by buprenorphine, but, of course, these days we do appreciate that there is some activation anyway, so they would be able to have some activity there anyway. Did I say that right, Andy? Okay, right, good. All right, so how would you approach this to him? It's an interesting question. How would you approach this to him? And you suggest, he already comes to you asking for buprenorphine, so what kind of questions do you think he might have that would be difficult to answer or? See, the question how would you approach this to him has to do with somebody who may be highly ambivalent or not wanting any medication for their illness. Just jumping a little bit on the side here, if that were the case, very often analogies with diabetes, analogies with chronic relapsing illnesses that need medication in order to stay healthy are very helpful. People understand that if they did have diabetes, they may need to go on insulin, that if they had hypertension, they may need to use an antihypertensive for some time. Depression also may enter into play, so this would be one way to present buprenorphine to them. But in this particular case where he is already committed, go ahead, in the back. No, wait, let me just take the first one in the back, yeah? Go ahead. I don't have an answer if he's already. So let me just paraphrase a little bit what you said, is that if you were highly ambivalent about it or not wanting buprenorphine at all, you can ask permission to provide the information, the potential benefits, the potential risks of what it is to expect for the medication. And I love that you brought up the issue of motivational interviewing. John is gonna be talking a lot about motivational interviewing later in the day, but motivational interviewing, a wonderful way of providing counseling and psychotherapy to our patients, particularly for patients who are in pre-contemplation or contemplation stage of change. Motivational interviewing tends to do its best job in those highly ambivalent patients or the ones who don't want to change anything in their lives. Just to take that one step further, not only we can work with patients who don't want to change anything in their lives through motivational interviewing techniques, in 2023 we have gone to the next level where we can even work with patients who refuse to come to see us. Somebody doesn't want to come to see us, but we can still use motivational interviewing and the way we do that is we bring in the family, we bring in loved ones. And what we do is we teach the family motivational interviewing techniques so they can apply those at home so they can move the needle and can move the patient from a pre-contemplation to perhaps a contemplation stage at which point the patient may very well come and see us. So there's no excuse, pretty much, to never work with a patient unless really that patient has no social contacts whatsoever and there is no family to even work through them to help our patient. Sorry, go ahead. Another very eloquent plug for the analogy with diabetes which, especially if the patient does have diabetes or has family members or friends who have diabetes, makes life a little easier, but even if they don't, it's just a common illness that people can understand the need for medication. I hope that depression will get to that level at some point, but we're not there yet. With depression, still there is, even if I have recurrent severe depression, at some point I hope that I'm gonna get off medication. So that's a work in progress. All right, let me move on here. Oh no, we have more comments on this one, the approach, which is a fascinating one. Go ahead. If you have a comment, why don't you go to the microphone? Maybe we'll be able to take that into the recording and so people don't just hear the same and the same voices. Okay, yeah, I'm an addiction addictionist and I also see Suboxone patient. I think for this particular patient, I think it's a good idea to start him on a buprenorphine treatment. What I think a couple benefit from harm reduction point of view. First, he's started using it daily during the weekdays that hinder his function. And secondly, the thing is that he wanna still use the hearing during the weekends. So by starting the Suboxone during the workdays, that it can prevent further function level decline because then he can go on with his daily job. And I think that's one of the important reason and outcome will achieve that preserves their daily function level. And secondly, consider the buprenorphine, the long hard life and the high affinity is that if he's taking the during the weekdays and over the weekend, he possibly don't have much of a craving and possibly use less of heroin if he indeed wanna use. And actually because of the high affinity, it protect him or reduced overdose risk. And eventually that can with, he's using the Suboxone or buprenorphine during the weekdays and eventually he might change his idea. I think, well, that's a better idea to use this Suboxone consistently. I'm so glad that you brought up this critical issue here. There is a paradox here. On the face of the story that we have in front of us, one can say, wait a minute here. If you're helping this person stop using heroin during the week, which is actually his goal, aren't you colluding with him to continue using a very dangerous substance like heroin over the weekend? Because then you make the motivation for stopping heroin altogether less so. I can have my pie and eat it too. One of those situations. It makes sense theoretically. In practice, it doesn't happen that way. Patients will come to me and have some kind of a plan of doing both and so on, end up much more on the side of seeing the benefits of treatment with buprenorphine and then giving up heroin and fentanyl quite possibly in this situation altogether. So I understand how somebody can have that objection here to this harm reduction approach. At least initially, but it does help in real practice. And once again, I'm gonna go to motivational interviewing. With motivational interviewing, just meets the patient where the patient is at and moves from there. You don't have to make a grand decision about what's gonna happen five years down the line. You can just work right now and then move with the patient along. Let me get another comment. Okay, go ahead. Oh, sorry. Go ahead, let's get to the, before we get to the repeat offenders. No, no, it's you. I concur and you said it so eloquently, but also legally and ethically, you know, they're adults, right? They can make their own decisions. They can make their own big boy bad decisions. And so as far as not doing the suboxone because they're still gonna use heroin over the weekend, well, that's their choice. But let them see how well they do during the week. And then it's their own decision, right? And so you're advocating for the patient and you're aligning yourself with them and you're addressing their primary goals, right? So you have that rapport that's established and then you go from there. But again, I back up everything you said. And then also legally, ethically, what they do on the weekend, again, it's their decision. Yeah, yeah, thank you so much for your comment. Okay, let me see if there's somebody else has a comment and then we'll go to the people who have already talked. But that's the deal. That's the process here. Anybody else? All right, go ahead. Thank you for that. I will have a problem in trusting this patient for a harm reduction unless I know some form of a support system who is willing to supervise. Okay, we're recording this. So you have to speak louder. You have to be no more than a minute and you have to be very clear with what you're saying. Okay. Go ahead. My role is to develop some trust with this patient for a harm reduction. Okay. This patient might have used to buying the Suboxone from the street, already using the Suboxone during the weekdays and then using the heroin during the weekends. So he may be using one or two milligram of Suboxone as an opioid agonist already. So he may be looking for a legal way of getting the Suboxone from a doctor. So he is also a multiple drug abuser. He goes to the venues where his friends are very enablers for his supporting his abuse. So my role is to develop a trust with him. I may involve his wife, but he is single. Any other family members who is willing to support the abstinence or at least a harm reduction first. Okay. Valid comment. People may disagree with that. It's just another way of approaching the patient. All right, let's move on to what aspect of his presentation might you use to point out his assets and liabilities? Okay, let me read that again. What aspects of his presentation might you use to point out his assets and liabilities? Let's just start with some of the assets here. What would be, what does, what's his name? Sean or, what was his name? Anyway, what, Mr. Smith. Okay, Mr. Smith. I'll call him Sean. What assets does Mr. Smith have? Sean Smith. Go ahead. Well, he's intelligent. He's a lawyer. He knows consequences. Okay. So he has somewhat intact frontal lobes and somehow analytical skills that will help him problem solve some things in his life. If he's actively working as a lawyer, we can make the leap of faith that he is cognitively not only intact, but perhaps significantly higher than the average person, and that is certainly helpful. There is such thing as defense mechanisms of intellectualization and rationalization, and we can play all kinds of tricks with our frontal lobes, especially if we're addicted to a behavior or a substance, but in general, it is an asset. I'm thinking about the stinking thinking of addiction. Remember, Narcotics Anonymous has talked about it long before neurobiology caught up with things. There is part, the medial or pedofrontal cortex that can very well trick us into thinking that we're rational human beings, while we're not. I did have a patient, a lawyer, who smoked in his room at the rehab and when confronted by it, he brought in the letter of the law and he said, look here, it says you're not allowed to smoke in your room or the bathroom. I was in the little ante room between the room and the bathroom that is not included in the rehab, you know, thing that I signed when I first came in. So there are ways of tricking our brains into different things. All right, go ahead. That, sorry. So I'm not a substance abuse person, but as a psychiatrist, he has an asset in a close relationship with a family member, his son. He's employed and he has a license and he doesn't wanna be disbarred. And in addition to his intelligence, he has a musical intelligence and is able to express himself beautifully and might be able to be encouraged to perform without being intoxicated or see what that experience is like. Fantastic comment. We can absolutely draw on his talent and expertise in music. We do that very often. We try to see what is it outside of addiction and outside your job and outside your family that really delights you and start to work with patients along those lines. Art is a huge one. Exercise is another very big one. A lot of our patients on one hand use all kinds of substances and addictive behaviors, but on the other hand, would love to be able to be more fit, be able to be healthier on the physical side. And we ignore a conversation about that while it would be an amazing in into a motivational interviewing style conversation with our patient. So certainly his art is an asset here. Yeah. He obviously is aware that he has a problem and that he's wanting to avoid the use during the week. My suspicion is that he may also be aware that the weekend use is still problematic. He believes in the treatment. He's got clients that are being treated. So that's the reason he's come to you. And I suspect that part of the reason he's using on weekends is social. Okay. So the issue of insight, I would characterize the inside here as fair. Like we tell our medical students on inpatient units, you never say inside good. You wouldn't be in an inpatient unit unless, you know, your insight was somewhat compromised. So I cannot say that his insight is excellent here, but I would say that it is fair because he is looking to help and he does want to go on buprenorphine. What about liabilities? What kind of liabilities do we have here? Okay. Is the support system being also used? Absolutely. The support group is also using. There is no husband or wife at home. There doesn't seem to be a major other support group, but he started the band himself and he gets his heroin from the people that he plays music with. So this is his family of choice in a way, his logical family, as Armistead Maupin would say, right here in San Francisco. And these people all use and provide him with the stuff. So that's an issue. Go ahead. I'm concerned for his teenage son also. Liability, why is that? He has a son, right? Oh, okay. Yeah, teenage son. So it would be risk for the son. What if son find out and accidentally use it? So there's a big liability. And also liability for his clients. He's a lawyer. So his executive function is really impaired. Poor judgment. So that's my comment. Thank you. I certainly see what you're saying with the liabilities. In some ways, think about the fact that these are also potential losses for him. So if his job means a lot to him, which seems like it does, and if his son means a lot to him, which we can assume that it does, it could possibly be somewhat of an asset in terms of making sure that he doesn't die, for one thing, that he doesn't get incapacitated, and so on. So in some ways, in terms of external motivators, in terms of coercion, external coercion, these issues may very well play to his advantage in the long run. Although, right now, they do seem quite a lot like liabilities. It reminds me of that biphasic curve of socioeconomic status with success in addiction treatment, where it seems that people from lowest socioeconomic strata and people from highest socioeconomic strata seem to be most difficult in addiction treatment, because either you've lost everything or you have so many resources, financial and everything else, that you don't have that much to lose, while people in the middle, in the middle class, where you have to take care of kids and you have to go to work and you have to produce and you have to meet deadlines, and pretty much the majority of us in this room, we may end up with a better outcome in addiction treatment. We certainly see that with impaired physicians who tend to do quite well with addiction treatment when there's so much to lose, license and well-being and welfare and the like. All right, I'm looking at my time here, and I see my colleagues, you know, nodding their heads, not so much in agreement, but more like, OK, Pedro, it's time to go here. So, what is your treatment plan for him? Other than, we've heard two major ones which work so well hand-in-hand, buprenorphine and motivational interviewing as strategies for this patient. Just to remind people once again that buprenorphine is the major ingredient in this treatment here. We have two and only two addictions for which we have done so well pharmacologically, tobacco and opioids. We've done well with alcohol, but not quite as well as with tobacco and opioids. And we have medications that are safe and effective that carry the burden of illness on their shoulders. And we absolutely need to communicate with our patients. If, at the same time, we can provide some psychosocial support, absolutely, more power to you. All of us would benefit from some psychosocial support. But never, ever make that a prerequisite for getting your patient on buprenorphine. We have treatment programs in the country where they say that unless you also come three times a week or blah, blah, blah for these kind of groups and the like, then you are not being prescribed buprenorphine. Terrible idea. Prescribe the buprenorphine, add the psychosocial support if congruent with the person's circumstances and if the patient really agrees to them. And with that, thank you so much and all the best to you. APPLAUSE How many of the audience are using buprenorphine right now or have done training before? OK, so most of you have. OK. That's good. But I'm going to start in a second with the initiation. None of this is new material for you guys. So, I'm going to start with the initiation. None of this is new material for you guys. OK, well, why don't we get started here? First of all, what is the point of this, to get people started on buprenorphine? We'll then move on to stabilisation and maintenance and talk a little bit about using buprenorphine for withdrawal treatment. Is this better? So, what's the rationale for buprenorphine? The overall goal is to help the patient switch from using full opioid agonists, whether legally or obtained from other sources, and to prescribe buprenorphine. The specific goals are to identify the dose at which buprenorphine for the patient causes them to decrease or stop. OK, so what is the goal for buprenorphine treatment? You're going to be able to suppress withdrawal symptoms, so you're going to make the patient comfortable. You're looking for a dose that has minimal side effects. You're looking for a dose that's going to diminish cravings, and looking for a dose that discontinues and markedly reduces the use of other opioids. It's fairly easy to control withdrawal symptoms, and that will occur at lower doses. Cravings may take a higher dose, and they may disappear from some patients. I think you'll learn as you use the medication how it's working for the patient. You want to look at the choice of the formulations, and to some degree this may depend on insurance or third-party payer preferences, the patient preferences, safety, and you may have some concerns about diversion. So, you have the optimal injectable buprenorphine now, but if you have a patient where you're very concerned about buprenorphine, that would be a good choice. So, what are the formulations? Sublingual film and tablets, which have been available for a number of years, and now the Depo injection. All of the approved forms have demonstrated very similar efficacy in the treatment of opioid use disorder, but note that the formulation or intravenous rebuckle are available only for analgesic use. They are not available for use for opioid use disorder, and technically the DEA does not want you using any of those formulations for patients with opioid use disorder. Now, this slide simply sort of spells out the specific formulations. The first group are the combo product, the sublingual formulations there, the film, the tablet, and their variable different strengths, which you can see. The monoformulation, generic tablet, sublicate, which is the subcutaneous injection, which is the newest drug that's available, and we're awaiting the release of the injectable bruxade, which would be available as weekly or monthly injections, but there's still a subdelay with FDA on approval, so that hasn't gone through yet. So what about the first prescription? How do you handle this? You can have the medication in your office, which I don't think anybody stocks normally, so you're usually going to give the patient a prescription. You've determined the patient can pay for it or will cover it by insurance. You confirm that they have a pharmacy that's available nowadays. That's not a problem. It used to be. And I would try to get a urine before their first dose, so you want to make absolutely sure that they've been using opioids and make sure whether they're using some other drugs of concern. You want to figure out how you're going to do this. So we have three options in the office at home or in the emergency room. And I think the emergency room is becoming more popular, and I think that people working in emergency room settings are becoming more comfortable doing this. So in the future, I expect that we're going to see patients who've begun in treatment in the emergency room and then are going to be referred to our office. And I think that's going to be a good thing. So that may be different options than we've been used to in the past. The role of telemedicine in all this, both in terms of your work in the office as well as in terms of work with the patient for home initiation is still somewhat murky. It looks like SAMHSA and the DEA are going to let us continue doing what we're doing right now at least for another six months. Whether there will be a long-term loosening, and one of the critical issues here is, we are now permitted to prescribe buprenorphine for the first time without physically seeing the patient. And whether that will be extended, I think, is the most critical decision we're waiting for from the government. How they do that and what the parameters will be, I think we will have to see what we can do. I think we will have to see what the DEA and SAMHSA say. So what about the first day? I would prefer to begin the patient early in the morning and prefer to start Monday or Tuesday. But this slide was originally put together before I think we were struggling with the public health emergency of overdoses and fentanyl. And I think that we're now working towards trying to start someone on buprenorphine the first day we see them, or as quickly as possible. And as I think we alluded to earlier today, most of the evaluation can be done after the patient has been initiated in treatment. I think you have to establish the diagnosis, so you have to get enough of a history to know that you can make the diagnosis of opiate use disorder. You should collect the urine so you know if you're using or not using. And then I would try to proceed with initiation as quickly as possible. So one of the things you're doing is, technically it's better earlier in the day because that gives you time to adjust the dose and change things later in the day. So I would prefer not to start people late in the afternoon. I would prefer not to start on Fridays. When at all possible, I would try to get the patient in as quickly as possible. The other thing is that you need to see mild to moderate withdrawal before you give the first dose. And the more critical thing there, and we're still struggling with this right now, is that because of the availability of fentanyl on the East Coast where I am, we don't see heroin anymore. Everyone is using fentanyl or prescribed opioids. They're coming in with syndromes that are perhaps more worrisome for precipitated withdrawal, but we'll talk later that that's probably not turning out to be as difficult a problem as we had anticipated. So I think we may be able to start the patients as quickly as we can. But I would basically look for moderate withdrawal symptoms before the first dose. I don't use a cow, so I've measured what's going on. And if you have any questions, start with a low dose. And you can always increase and give more if the patient needs it. Now, these are the general parameters that we use in terms of patient instructions depending on what they've been using. If they've been using street opioids, heroin mainly, the normal direction is wait 12 to 16 hours before you begin initiating the buprenorphine. If it's a prescribed opioid, 24 hours. If they've been on methadone, about 36 hours. That being said, what do we do with fentanyl? And there I think we're still learning how to do it. I think it's turning out to be more common than we ever imagined, but it's also turning out to be a little easier to override the fentanyl with buprenorphine when you start an induction. And I think in the beginning we were afraid you couldn't do that at all. But I think that it's easier certainly if you make sure the patient is showing you moderate withdrawal before you give the first dose. This is the cow scale. I'm sure you've all seen this before. Mild is a score of 5 to 12. Moderate is 13 to 24. Or 25 to 36. And the fear is over 36. Generally what we're looking for to start people most of the time would be moderate in the range of 13 to 24. It's also very important to instruct the patient on how to take buprenorphine sublingually correctly. Often patients are not doing it correctly and that may result in inadequate absorption. So they may tell you the drug isn't working or you're getting less of an effect than you expect. And that's simply because they're not taking it correctly. So they need a moist mouth. You need to avoid acidic drinks, no coffee or fruit juices before you take the first dose. Avoid nicotine products because that may interfere with the patient's ability to speak. You don't want them to speak. You want them to simply hold the medicine under their tongue until it dissolves. And once it's dissolved completely they can either swallow it or spit out the remaining sputum. But just make sure that they understand how it is done. If the patient isn't in opioid withdrawal, what do you do? You can wait. You can have them wait in your waiting room or come back. You can spread it out during the day so you can see them again later in the day so you can have them wait. Or you can send them home for a home induction. We used to say send them home and come back and start tomorrow. We're not really doing that anymore. I think because we want to get patients started we're more likely to send them home and give them meds to take home with them Years ago, buprenorphine was not that common among the patient population so they didn't know how to take it correctly and it was a little bit of a problem in terms of letting them self-induce at home. Nowadays, most patients have used buprenorphine and they've been on treatment before or they know how it works. So once you've just carefully instructed them it's proving to be pretty safe and comfortable to do a home induction. The way I would normally do things I would write prescriptions if I'm going to send the patient home for maybe two days of medicine, three days of medicine and plan to get them back or plan to talk to them over the telephone in the next two or three days to help them adjust the dose. But I would like them to either start medication while they're in my office or leave the office with a small prescription to take home so they can induce themselves at home. So patients who are on short-acting opioids you want to do what I've just described instruct them how to do it wait until they're at mild to moderate withdrawal which is at least over 8 document the severity of withdrawal and then start the medication. They're less likely to have any precipitated withdrawal if you wait until they're really showing more mild or more moderate symptoms of withdrawal. But I think one of the problems with fentanyl is there's a lot of erratic discharge from adipose tissues with fentanyl so patients may look okay, and then later they may have higher buprenorphine levels and they precipitate withdrawal. So it's a little hard to predict what's going on. And we're looking at new techniques for using higher doses to handle patients for withdrawal. We'll probably talk more about that in the update talk tomorrow. But there are techniques now for handling initiation with either low dose or high dose that give you an alternative to begin patient. Really, we did not have that as initiation from the beginning. Generally, we would like, it's probably safer to start with lower doses and go slowly, but that doesn't mean you have to wait a week. You can probably go slow and get a patient up to a blocking dose within a day or two days. So you're able to get the patient onto a safe dose pretty quickly. Now, this slide shows some of the variations that are related to the presence of fentanyl and options you might have in controlling the symptoms that you would be concerned about with fentanyl. First of all, what we're calling low dose. And you see in that slide, the patient has been on fentanyl for a day. You're waiting two days, give them a little bit of time to wash out the fentanyl from their system, the heroin from their system. You may start them on symptomatic treatment with other medications, which is that block at the top. And then you see over the next two days, that's a very rapid induction to a high dose of buprenorphine, but starting at a low dose. And that might be a quarter of a film strip. And you might give them one dose. If they do all right, wait a couple hours, give them another quarter, another two hours, you may give them a full half. And you may be able to get several film strips into them over the course of the day, so that you're able to get up to 16 by the end of the second day. Now, this is a high dose method. This is what is mainly been using in emergency rooms. This is a more challenging method, and it is problematic in the sense there's a potential for overdosing the patient. And I think that it probably can be done in the office, but I would not recommend that you do it in your office. I think it should only be done in a hospital emergency room where you can contend with any problems. But here you see the patient has been bit on fentanyl. They give them one day for no medication, and then they start rapidly inducing buprenorphine in the course of one day. And again, their target dose is 16 milligrams by the end of the first day. So this is a different recommendation from what we made 10 years ago or 20 years ago, where we're usually aiming at eight milligrams the first day. Here they're going up to 16 in the first day. But again, I would stress that I think in almost every situation in which this technique has been described, it's been conducted in an emergency room and not in a non-patient setting. And then last, there's a crossover technique. And here you see the patient is continuing to use fentanyl for six days. But they've started with a very small dose of the buprenorphine, and they gradually extend that dose over the week. They gradually build that up. So they've got an overload here. Now the problem here, ethically, where is the fentanyl coming from? I mean, we can't prescribe it to the patient. It's very awkward to be in a position of recommending that the patient continue to use fentanyl while you're giving them the buprenorphine. But that does permit you to do this crossover, which is another way of getting the induction done. Now just to review the techniques, starting with first dose should be low, two or four milligrams. If you're trying to do this taper with very small doses and rapid escalation, you would try to get a film strip and use it in small quantities. You could, if you had a compounding pharmacy available to you, you may be able to get buprenorphine, or you can break up the tablets. It's a little harder if you're doing quarter tablets or half tablets, but that could be done. You wanna monitor the patient after the first dose. Two hours later, it's safe to give them a second dose. If you start it early enough in the day, that gives you a fair amount of time where you can keep dosing the patient every two to four hours, particularly if withdrawal symptoms continue. Your dose would be at least eight milligrams the first day, and now with higher doses, going up to 16 milligrams the first day. Once you get the patient to that dose, you probably should wait, and wait several days, if not a week, before increasing to higher doses. Though in some emergency room settings, they've been going up as high as 35 or 32 milligrams that first day, so if you're at a place where you can contend with the consequences of overdosing a patient, then you can go quickly. But I certainly wouldn't recommend trying anything like that in an outpatient office. It would be dangerous. But people are struggling with these protocols. There's no one standard way that's recommended. There's no real research in any detail on most of these protocols. There has been some research published on the emergency room use of high-dose initiation, and it's shown so far that it's safe and works well, but it's not the situation that's available to most of us. So I think I'll stop at this point and turn things over to Dr. Saxton. Andy, do you want me to stop for questions? Yeah, I guess I have a question in terms of induction via telehealth. What is common practice? Via telehealth? Correct. That's what we were talking about earlier. Well, that's a very good question because there is no documentation of what the common practice is or the protocols people are using, and telehealth, per se. I think they've been using the techniques that we're describing. I would presume the more standard, older, office-based or home-based with the smaller doses. I don't think anybody is using telehealth with high doses or large doses. I think that's restricted to this. But I mean, logistically, are we telling patients to take two milligrams every two to four hours whenever they feel withdrawal symptoms? You're instructing them to take two milligrams. If they feel fine, they can stop, period. That's good. I mean, that's probably unlikely, but you could stop. If they're still having more withdrawal symptoms or the withdrawal symptoms seem to be getting worse, you can take another two milligrams and then you can wait another two hours and you can take another two. So you could gradually increase over the course of the day. That answer your question? So telehealth initiation, it's gonna be home initiation. And there are actually apps that could actually guide the patients through about checking through their withdrawal symptoms and when is the right time to start the first dose. So I primarily work in VA, so I'll overnight the medication to their home residents. I do ask them to, if you're gonna start them, I prefer not to be on a Friday evening because I'm not gonna be in the office to answer any questions that come up on Saturday or Sunday. But here's an app, or if it's during the day, I ask them, it's probably better to start the first dose in the first thing in the morning while we are still working, so you can actually call us. But there is an app to kind of guide patients through, like to monitor how much withdrawal symptoms they are in and when is the right time to take the next dose. Yeah, I think as a bottom rule, if you're doing it by telehealth, I would be conservative. So I would tell them, you know, don't go over eight milligrams the first day, no matter what, you know, and maybe we can increase it the next morning, but maybe we can get on telephone and talk to them or see them again and try and do it, make some judgment. But I wouldn't be cavalier about letting the patient self-induce with large doses on their first day or no one's around to watch what's happening. We're gonna cover some of the areas that Dr. Renner touched on in more detail and ideally answer some of the questions. It might be a little repetitive. If so, tell me and we'll jump forward. So what happens if we have precipitated withdrawal? And we used to say that almost never happens if you do the initiation properly and observe enough withdrawal, but there's at least anecdotal information that with fentanyl, it's more likely to happen. So we may be confronting it more frequently. There is a study that came out in the last month or two where they did something like 800 initiations in emergency departments. About 60% of the patients were positive for fentanyl and they only had a handful of cases of precipitated withdrawal. So the data we have suggests it's not all that common. But if it does happen, what you will see is not the withdrawal getting mildly worse, which probably means you didn't give enough and you need to give more, but getting very instantly, dramatically worse. Just as a question, how many of you have been working in an ED in your training or something and someone came in with an overdose that got reversed by naloxone? Has anyone observed that in an ED? A few of you. Well, that's what precipitated withdrawal really is. So you go from almost being dead to suddenly having severe withdrawal with profuse sweating, vomiting, diarrhea, tremor, that sort of thing. And so if you have precipitated withdrawal, typically it's gonna be a big increase. So the two choices are, which really aren't a choice anymore, is stop the initiation, let the patient go home or even if they're at home, stop it and then try again another day when they're starting with more baseline withdrawal. But we don't think that works too well and what we think the best procedure is in 2023 is to power on through and just keep giving more buprenorphine. It might make the precipitated withdrawal worse at first but once enough of the receptors get occupied, it seems to us like that alleviates the precipitated withdrawal, assuming the patient's willing to do that and then they're on buprenorphine. We talked a lot about home initiation. I'll just give you my take on it. In our program, I don't think we've done an in-office initiation except under rare circumstances in the last eight years because we're having good luck with home initiation. That does help with what Dr. Park was saying about getting the patients started the day they come in because if you're gonna do it in office, they have to get the medication, bring it to the office, you have to have an appointment time available for them, that could delay things a few days. If we do home, they come in, we do the quick evaluation, postponing the details of the evaluation for later, the comprehensive evaluation. They get a prescription that day, they go home and they can start whenever they're ready. What I do is I actually try and educate the patient about the difference between symptoms and signs and so I tell them it's not enough to feel bad that's the first thing that's gonna happen when you go into withdrawal, you're gonna start to feel bad. You have to look at your own body and see that things are changing. So it might be that sweat is pouring off of you, it might be that you develop a tremor, it might be that you can observe goose flesh, it might be that you can see that your nose is running or your eyes are tearing or you can see that you're coughing. So they can learn that and when they start to develop the signs, that's the time to get started. Just on a very, I do things a little bit differently than Dr. Renner because at least in our setting it's not that easy for the patients to come back two or three days later so I usually, and this is just, this is not like the cookbook the way you should do it, just sort of my approach and you figure out your own approach. I usually give a week's worth of medication. So if I'm using tablets or film, I'm gonna give them four two milligrams for day one. I'm gonna give them an extra eight milligrams for day one that they may not need but they might need and then I'm gonna give them two eight milligrams for the subsequent six days assuming that most patients are gonna need at least 16 milligrams to stabilize. They can always take less and then that way most patients will have enough medication to get them through that first week and I'm gonna have some telephone or if they have the capability, video follow-up with them during that week to see how they're doing and I will tell them to, when you're ready to start, you have signs of withdrawal that you observe in your own body, take two milligrams first and then just as Dr. Renner said, every couple of hours if they're still having withdrawal, they can take more. Probably stop at eight milligrams on day one but if the withdrawal's still present, they can go higher and then see how they're doing with 16 per day if they need that much in the subsequent days. If that turns out not to be enough, you can always then bring them back in before that week is up and give them a new prescription. So I think we kind of already covered day two so we're just gonna keep getting up. Yes, there's a question back there. Yeah, come to the mic, great. Just wondering if clinically you've ever seen precipitated withdrawal with the home initiation and if you do, what do you do in that case? Are you bringing them into the eMERGE or are you doing? Oh, if they have precipitated withdrawal. Yeah, we don't see it often. The one thing I will say is if you have precipitated withdrawal, it's very, very miserable and I think it's gonna be better for the patient to be at home if the patient needs to use the bathroom from both ends frequently. It's a lot better than trying to do that in a public bathroom so I think that's good. But again, we can bring them in. I would encourage them to continue their buprenorphine if they need more, like they need an alpha-2 agonist or they need something for nausea or diarrhea, yeah, they'd have to come back in and get other prescriptions or we'd have to call in those prescriptions that they could pick up. So I think you can partially manage it over the phone. If it's extremely severe, then these patients probably do need to be admitted and we end up doing something like giving them some benzodiazepines over two or three days in the hospital that just basically sedates them enough that they're not as aware of how horrible they feel. But most patients are gonna be able to get through it at home with some comfort medication and continuing to up the buprenorphine. Thank you. Okay, so we're just in touch with the patient and as you've heard, we're gonna go up to the dosage and I'll talk to you in a moment about how to determine what, or my approach to determining the optimal dosage. Oh, okay, I'm gonna talk about it right now. So stabilization, it says eight to 16 milligrams per day. We're probably, in the fentanyl era, we're probably more in the range of 16 to 24 milligrams per day, at least that's my experience. I'll just say, Dr. Renner said it's all fentanyl on the East Coast and we, in Seattle, we were a little bit lucky that we had a couple of years of reprieve and we could watch all of you struggling with the fentanyl. Now we're all fentanyl. Some, apparently there's some secret supply of heroin that some of the older patients have figured out how to get and actually a lot of them say, even though fentanyl is supposedly more potent, a lot of them prefer heroin, but sometimes they can't even get heroin, so they're using fentanyl. So what are the, how do we determine what the right dose is so for me, that's four or five questions that I ask every patient every time I see them. The first thing is, are you having withdrawal symptoms? If they're having withdrawal symptoms, then we know that they're at risk to use illicit opioids because withdrawal is a very intolerable state. If they're having withdrawal symptoms, we probably need to go up in the buprenorphine dose. Second question, are you having cravings? They say no withdrawal, but are you having cravings? I already mentioned earlier this morning, cravings are associated strongly with outcomes. So if they're having cravings, we want to suppress those. Probably need to go up in the buprenorphine dose. Third question, you may or may not see this on a urine test and we hope we have good enough rapport with our patients that they're gonna be honest with us and if we shame them about using illicit opioids, if we shame them for doing the behaviors that are associated with the disorder that they have, they may not tell us, but if it's open and honest, good therapeutic alliance, have you been using opioids? And they say yes, they probably need to go up in their buprenorphine dose. Sort of 3A is, oh, you used an opioid, how much did you feel the effects of that? If they say, I used it, but I didn't feel anything, we have a pretty good indication that we have enough receptor occupation that they're not feeling much. And that's analogous to what I talked about about naltrexone blocking the effects and that extinguishing the use. So maybe if they're not feeling it, we don't need to go up. If they're feeling it, we probably do need to go up. And then the final question is, are you having side effects? If they're having side effects that we cannot manage or that are intolerable, it might be a situation where you need to decrease the dose. So those are the questions I use to determine what is the optimal dose. And so if we get to the right dose, no withdrawal, no craving, no illicit opioid use, manageable side effects, if any, then we're where we want to be. Okay, so we've been talking a lot about fentanyl. We all know that that's the issue we're dealing with. We kind of got blindsided by it because fentanyl was developed in the 1960s as a parenteral treatment for acute pain. And when the pharmacology and pharmacokinetics were studied, it was all about short-term use. During the early 2000s, there were the fentanyl patches and the fentanyl lollipops, much lower amounts of fentanyl than what people are getting with the street fentanyl now. And so what we didn't realize is even though it has a short half-life, it is so lipid-soluble that it's getting stored in fat. And so that's why, even though it's technically a short-acting opioid, sometimes 24 hours or 48 hours off of fentanyl, there's still going to be plenty of fentanyl being leached out of adipose tissue into the bloodstream. And that's making it tricky, and that's why we think that sometimes there's difficulty with initiation. So it does say, and it's true if someone's inpatient, especially if they have pain, you could give them a few days off of fentanyl and put them on a short-acting, full agonist opioid like morphine, and then if you're initiating buprenorphine, it's more like the old days, you're going from a short-acting, full agonist, where 12 or 24 hours of abstinence, you can start the buprenorphine pretty easily. So we're going to talk about the alternative methods, which John Renner alluded to. So the reason they did this in ERs is because, as we all know, they don't have a lot of time with the patients, and if they start them on buprenorphine, they don't know what their follow-up's going to be. So they have studied starting even at 8 milligrams or 16 milligrams as the first dose, and going up to 24 or 32 total on day one. And so the objective there is, one, if the patient doesn't get an outpatient appointment promptly, they have enough in their system to last two or three days. And number two, they want to quickly eliminate the withdrawal while they're still in the emergency department. This is found under monitoring to be largely safe and not a lot of cases of precipitated withdrawal, although they're monitoring people very carefully. And so that's been found useful. Now I'm going to talk about another technique that's totally off-label, so be aware of that. But John Mariani at Columbia has done a small open-label observational study where he's given up to 24 milligrams sublingual on day one, and then he gives an injection of a long-acting depot of 300 milligrams. And he has had, it's only a handful of patients so far, but he has had really good success with that, not seeing precipitated withdrawal, and getting a good amount of buprenorphine into the system on day one, and also then having patients, since it's a 30-day injection, having patients with buprenorphine in their system for a month so we don't need to worry about are they taking it, did they take it, how much should we give them, et cetera. So that's, if you want to go off-label, that's something, and be bold, that's something to consider. I'm not recommending it, but it's out there and we'll learn more about it. Okay, and then we talked about the low-dose crossover. So this is a little more common than the high-dose. I do have colleagues who say this is what they've been routinely doing to initiate patients who are using fentanyl. How many of you in the audience here have used this low-dose crossover? A few, not many. This just gives you an exact recipe of one way to do it, and John Renner pretty much talked about that. So you do have to, one of the tricky parts here is most pharmacists are not going to put on the prescription label, cut your film in quarters. So it's a little uncomfortable and awkward, but you have to write the prescription, start with two milligrams, and you're telling the patient to do something a little different than what the label on their bottle says. Is that what you end up doing, DC, or? Maybe I shouldn't speak into the mic. No, speak into the mic. I mean, you know, we're among friends here. I don't see, are there any DEA agents in the audience? So just to caution you, so buprenorphine patch, the brand name is Butrans in the United States and it is not approved for opioid use disorder. However, it is approved for chronic pain and there's a DEA law that allows you to, there's a three-day exception rule where you are allowed to prescribe a short-term full agonist opioids while you're in the process of getting them to long-term treatment. So the benefit of using buprenorphine patch is that the, so I don't have to worry about cutting the tablets into quarters. If I'm cutting them in quarters, I will use the films because it's easier to cut them more accurately using the films. But yeah, using the buprenorphine patch, its peak level is reached 24 to 48 hours after. So I'm using the 20 microgram per hour formula that delivers about 0.5 milligrams of buprenorphine in 24 hours and their peak level is reached 24 to 48 hours after as opposed to tablets or films where, you know, they're reaching their peak levels in two to six hours. So it gives me that added benefit of just even slower, more gradual, you know, titration of buprenorphine to bind to the opioid receptors without, you know, minimizing the risk of perspective withdrawal. And then on day three, I have to, you know, I have to take off the patch and start the two milligrams of buprenorphine tablet or films and that has worked out fairly well. That sounds like a great system. So the alternative, what I've done is I'm just telling the patient, do this a little differently than what the label on the bottle says. So they would have to cut their two, since in the U.S. two milligrams film strips or tablets is the lowest dose available, they're going to have to cut it in quarters for the first two days and then in half for day three if you follow this algorithm. And you can see it, you gradually increase and by day six or day seven, you're up to 12 milligrams, no precipitated withdrawal, then you just tell them to stop their fentanyl and then you can proceed up with the buprenorphine dosage as needed to optimize the dose. You have a question? Okay. So the, we say once a day dosing is fine in my, and that's what we should encourage. The advantage there is the patients aren't constantly thinking about their medication, they take it once during the day, they go on about their lives. If the patients, and particularly the patients who have chronic pain also, they do prefer the divided doses, but for some reason some patients like taking it twice a day, sometimes three times a day. I don't struggle with them about that, I mean even if I said you must take it once a day, they're going to go home and do what they want. And it's sort of physically impossible to take a bunch of tablets or film strips at one time, so if their dose is like 24 or 32 milligrams, they're going to have to take the medication sequentially even if they try and do it all once per day. We already talked about how to adjust the dose. And we've already talked about how long maintenance should be continued, so you know my bias is indefinitely, although if patients say they definitely want to get off of buprenorphine and I've talked to them about the risks and benefits and they say yes, I still want to go ahead, then I do work with them to help them gradually taper down. And what we often see is they hit two or four milligrams per day, and they've done fine until then and then they do start having some withdrawal symptoms and it's really hard to get off that last bit and that's when I may come back to them and say, you know, if you're on four milligrams or eight milligrams, you're getting a prescription once a month, we can even mail it to you, it really isn't having a big impact on your life, it's okay to just keep taking this medication, and so that's often what they do decide to do. And you've seen this already that early tapering leads to bad outcomes. So we'll talk about, we've covered most of this, we'll talk quickly about the naltrexone. It is expensive, if insurance doesn't cover it, it's frustrating, if this were a medication to treat cancer, another lethal illness, no one would blink twice for spending $1,000 a month, in fact sometimes we're spending $25,000 or $30,000 a month, which we should do, but I don't think $1,000 a month to save a life is that much. Insurance sometimes does cover it, you'll have to order it from a specialty pharmacy if you're in private practice and get it delivered. If you're starting it, we talked about the seven to ten days opioid free needed, one way that you can check if patients are ready is to do a naloxone challenge test, has anyone done a naloxone challenge test? A couple people. So the reason for that is naloxone has a very short half-life of about 90 minutes. So if you give someone naloxone and they have precipitated withdrawal, you know they're not ready to take naltrexone, which has a much longer half-life, especially the injection form. So then you wait a few days. So the way you do that is naloxone, now we have the nasal spray, and honestly I haven't done one of these challenge tests using the nasal spray, so I usually have done them with parenteral naloxone, which you can give either sub-Q, IM, or IV, and you give usually a dosage of .4 milligrams, say IM, and you wait 45 minutes. If there's no precipitated withdrawal, they're probably ready to take naltrexone. Or you could just try the oral naltrexone. If you precipitate withdrawal with the oral naltrexone, it's still pretty bad, because remember it has a four-hour half-life, the parent, and the active metabolite has like a 12-hour half-life. So people are going to be sick for probably a day or a day and a half, two days. So I like the naloxone challenge test, unless I'm really confident the person has been 10 days without any opioids. And of course you want to warn the patient, if you've been using opioids any time in the last week, you're probably going to get very sick if I give you this medication, so honestly tell me. Let's see. I think we've covered all this. So we have to do the withdrawal management. Actually this slide we've already covered, so I'll go over it again very quickly. You can start them on buprenorphine, taper that down, wait 7-10 days, start the naltrexone. We can use the clonidine and other comfort medications for 7-10 days and start the naltrexone. And then we have this newer approach, which actually they just did a randomized trial on an inpatient setting, and they found that this was more effective than treatment as usual, which is the combination of some buprenorphine for the first couple days, then clonidine and benzodiazepines, not very high dose benzodiazepines, a little bit, and then starting with these very low doses of naltrexone, like 2 milligrams or 4 milligrams that you have to get from a compounding pharmacy. So I don't think that's practical for most of us now, but it did work better at getting people on naltrexone if that's your goal. So yeah, if people are on naltrexone and they develop acute pain, either from an injury or an acute medical problem like appendicitis or acute pancreatitis, we're going to have to give them a lot of full agonist opioids to override that blockade under very careful monitoring so we don't overdose them in the hospital. And then there's some nuisance side effects. Nausea is probably the primary one, and that usually gets better just with time on the medication. So if you start the injection, patients might have a little nausea at first. By the end of their first 30 days, they don't have it and they've kind of forgotten about it. It is a very deep intramuscular gluteal injection, so it can be painful to give it and also some residual pain after the injection. The injection technique is extremely important. The mistake that people make is going too shallow and injecting it in the subcutaneous fat. That's when people get the injection reaction. So good to have a nurse, or if you want to learn to do it yourself, that's fine as well. I've given a number of these injections myself, and I'm pretty – I remember the days when I gave gluteal injections of procaine penicillin, and I got really good at going deep, right way into the gluteal muscle, but the nurses need to know how to do that. If you're too timid, you're going to end up thinking you're helping the person and getting an injection site reaction. So finally, we've got acute withdrawal, and in my opinion, really the only reason to do opioid withdrawal for someone with opioid use disorder right now is if the patient says, I want to go on naltrexone. If the patient doesn't want to go on naltrexone, then we should be using 99% of the cases either buprenorphine or methadone. Now there are some patients who are going to say, I don't want any medications, I just want to be withdrawn. I don't see too many of those, but I guess that would be another scenario where you're going to do this. And I think it was mentioned earlier by someone, you don't have a lot of patients on the naltrexone injection, and that's true in our program too. We don't have a lot of patients who say, yes, I'm willing to go through seven to ten days of withdrawal to get on this naltrexone. But there are some patients who do want that and do well with it, as we've seen. So we can use the clonidine and the other comfort medications. We talked about adding the naltrexone at low doses. If we're going to use buprenorphine to do acute withdrawal, just here's one algorithm, get them up to 8 or 12 milligrams on day one, and then quickly taper that down over two or three days, or extend that. If we're, again, that's a short-term solution because most people are going to relapse. We've talked about the termination from maintenance, and that would be a very gradual reduction over weeks to months. And just to be specific about the comfort medications, again, the alpha-2 adrenergic agonists, which I assume most of you are familiar with, and clonidine is the prototype. So the alpha-2 receptors are autoreceptors that are on the presynaptic neuron, and what happens in a normal situation when there's enough norepinephrine in the synapse, it binds to these autoreceptors and it tells the presynaptic neuron to turn off norepinephrine release. So clonidine and the other medications, lofexidine, we're actually using clonidine off-label because the indication for clonidine is high blood pressure. Lofexidine, which is very similar, actually does have an indication for opioid withdrawal. I have a colleague who uses tizanidine. You could really use any one of these that you're familiar with. But a lot of the withdrawal is driven by a hyperadrenergic state, and by using these alpha-2 agonists, we can turn off norepinephrine release. Insomnia is very common, so I think trazodone is a good solution. Some people do use short-term benzodiazepines or other sedating medication, but if we're trying to do this and the patient isn't sleeping, the patient's probably going to quit. Acetaminophen or ibuprofen for the pain, that helps a lot. You could also, if you want to get more aggressive, you could use catoralac. Sometimes for the muscle spasms, benzodiazepines do help. And again, it's up to you whether you feel comfortable doing that short-term or not. And then we've got, in my experience, ondansetron is great. That's another medication that does prolong the QTC, so just be careful about that. And loperamide works well. So I like to pretty much be aggressive and load patients up with these medications. It's much better to intervene quickly with withdrawal than wait until it gets too bad and it's really hard to catch up with it. Okay, so here's the summary. So we want to... Whoops. Well, it doesn't matter. I'll give you the summary. So we can start naltrexone after 7 to 10 days. We recommend using the long-acting injection over the oral. And we recommend very rarely doing short-term withdrawal unless we're starting naltrexone. So I think we should have time for questions. I actually have more of a comment. I work in corrections in California. I work in corrections in California and there's a big push to start buprenorphine and treat opioid use disorders in the correctional setting. Some people are... Some inmate patients are not in withdrawal. The starting dose ranges anywhere from 8 to 16. There is no gradual titration up from 2 milligrams and adding every 2 hours. And psychiatrists cannot prescribe buprenorphine in the correctional setting. It has to be the medical doctor. And diversion is huge and then the withdrawal happens after they take a few films sublingually and then they start diverting it and then that's when the trouble happens. So if I understood the question, this is using buprenorphine in the correctional setting and you said they don't have withdrawal. So are you saying because these people have been off of opioids for so long, they don't have withdrawal? Or are you saying they're using illicit opioids in the correctional setting and they're just given buprenorphine? I mean, I'm not sure what the... Both. Both. Okay. Well, so that's a good point. I don't think we talked about this. Dr. Park mentioned starting buprenorphine, or maybe that was, I guess that was actually Petros Lavounas, starting buprenorphine on someone who'd been off of medication for six, off of opioids for six months but was fearing relapse. If you were starting a patient who is not currently physiologically dependent on opioids, you do have to be careful by going up too quickly because they can get a lot of intoxication. Of course, the experts always do something wrong first. So I did have a patient who was, this is years ago, but she had been misusing prescription opioids but she had stopped. And she drove to the clinic, which you should tell the patient, if you're going to do any clinic induction, the patient shouldn't drive themselves. But I made this mistake. I gave her just 2 milligrams and she looked fine, but on the way home she got pretty intoxicated. So if they are currently not physiologically dependent, start very low and go very slow. I mean, if they're giving it to people who have opioids on board and they're giving them 8 or 16 milligrams, then yes, they're going to probably get a lot of precipitated withdrawal. In terms of the diversion in that setting, they can do observed ingestion, but better yet, they could switch to using the injection and then there wouldn't be any possibility of diversion. So that's what I would recommend. Is any changes in the detox protocol, buprenorphine, if the patient is withdrawing from the alcohol? We start him to detox him on Ativan, so is any changes in the protocol how to detox him from opiates as well? Sorry, I had a hard time, you said something about Lorazepam? Withdrawing from alcohol and also from opiates. So they're withdrawing from alcohol and opioids at the same time, like in an outpatient setting or inpatient setting? Inpatient setting. Inpatient setting, yeah, so what I would prefer to do is stabilize their, I mean, there's this belief that opioid withdrawal is not a lethal illness, and that's largely true, but there actually have been some deaths in people who have medical complications or even people who are healthy who are vomiting so much that they get aspiration pneumonia. So, but it's certainly true that alcohol withdrawal is a more serious condition. So what I would prefer to do is not to try and treat both of those at once, but stabilize the opioid withdrawal with buprenorphine and then do alcohol withdrawal. And then if they need to come off the buprenorphine, you could attend to that later. I don't see, check with my other two colleagues or anyone in the audience. I don't see how I could comfortably withdraw someone from opioids and from alcohol at the same time and really know what's going on and ensure that I'm not going to get complications. So if I may comment, I get questions from the inpatient side. So there are multiple different case scenarios. If someone has been on stable buprenorphine maintenance and they had additional alcohol use disorder and they decide to come in for treatment. And the question would be, what are we doing for their buprenorphine dose while we are providing with the benzodiazepine for alcohol withdrawal management? With that particular case, I tell them, look, they've obviously tolerated 60 milligrams of buprenorphine and a high amount of alcohol, now they're in a safe inpatient setting where they're getting the COR every four hours. If their buprenorphine dose tends to be on the higher dose, 24 to 32 milligram, temporarily dropping them down to 60 milligram is not going to make too much opioid withdrawal for them. And I would advise them to just keep the, I would prefer to keep their alcohol withdrawal management just symptom triggered, PRN only, COR driven, using shorter acting benzodiazepine instead of long term taper of a chlorodiazepine side. Now if there are patients coming in for both alcohol and opioid withdrawal, then that gets a little bit more complicated because if they're withdrawing both from fentanyl and from the alcohol, we don't want to mask the symptoms of like a benzo withdrawal or alcohol withdrawal. There are some evidences that the benzos can actually make them a little bit more comfortable during the opioid withdrawal, as we've seen in the naltrexone, long intake naltrexone initiation. So I prefer, in that case, I prefer to let's make sure that they're not going to require high dose of benzos, like in other words, we're not going to have to transfer them out for ICU evaluation because of DT or seizure. Let's get them through alcohol withdrawal, observe them for 24 to 48 hours, make sure that they're not going to be in a very complex alcohol withdrawal, and then we can talk to them about starting buprenorphine at that time. So that's been, you know, what I've, that's been what I've been doing. Thanks, D.C. Other questions? D.C., would you mind answering because I had a really hard time understanding the question. His question was that even by using the microdosing initiation of naltrexone, using the compound pharmacy, one milligram, three milligram, and by the fourth day, he's cutting up the 15 milligram tablets. Even with that, patients are having perspiratory withdrawal symptoms on the third and fourth day after getting the compound pharmacy. Right. And, you know, you know, personally, I, you know, I can tell you that the, you know, you're lucky to have compound pharmacy. I don't have access to the compound pharmacy, and we haven't, I don't have much experience using low dose naltrexone. I don't know if, you know, Dr. Renner or Dr. Saxon have, or anyone from the audience. Yeah, I had some experience years ago, and we were splitting the tablets like what you're saying, but the lowest dose we could get down to was 6.25 milligrams. And so you saw from the slides, you're talking about two or three milligrams, which is half that, and you just can't split the tablets that clearly, so you would need a compounding pharmacy. So I think starting at 6.25, which is one quarter of the tablets, is probably going to be difficult. It's probably too much to get started with. So I wouldn't strongly recommend that unless you want to be dealing with a lot of precipitated withdrawal. So it's not, and it's not, it's really not fun for the patients, but it's not very fun for us either to make patients feel sick. And sometimes they don't like us as much after that. Most pharmacists will split tablets for you if you ask them. They have tablet splitters. So if you need to get a lower dose, you can ask the pharmacist to split the tablets. Yeah. Okay. So the lowest dose that comes, the naltrexone comes in the U.S. market is 15 milligrams. And, you know, after, you know, you cut the medication in half, our pharmacists don't advise cutting them into quarters because the dose, it's not going to be consistent. So, yeah, you know, my experience with the pharmacists have been, you know, somewhat different. You know, I can just add that the, it's probably, you know, coming from like, because of the more fentanyl and that tends to be longer lasting. When they did the, the low dose micro, you know, micro dosing initiation of naltrexone, they probably were dealing with more heroin. And my guess, you know, again, you know, I don't have much experience with that. My guess would be that you gotta, you gotta wait longer and you gotta wait even slower with the low dose naltrexone. Are you going to address xylene later in the presentation? I'm sorry. I can't understand. I can hear, but. Are you going to address xylene later in the presentation? Xylazine. I don't know that we have that. We are going to address it tomorrow, but we can, we can talk about it. We have another five minutes or so. We can talk about it now. So how many people are familiar with xylazine? Okay. A few. So this is relevant to what I said about the alpha 2 adrenergic agonist. Xylazine is a extremely potent alpha 2 agonist. It's going to turn off norepinephrine release. It is approved for veterinary medicine and the veterinary, especially large animal veterinarians say they absolutely have to have xylazine because it works very well to keep the large animals sedated while they do various painful procedures. And of course we know, I mean, if you try and do anything to an animal to which you cannot explain why you're doing it, the animals are going to resist. And so the supply of drugs is now being cut with this xylazine. So the cartels have somehow figured out that either they can use this xylazine and put it in with fentanyl and it's going to increase the high or it's going to prolong the high or it's cheaper than the fentanyl so they can get away with that. It's unclear why they're doing it. But the problems with xylazine are humans can overdose on it and naloxone is a great reversal for opioids and maybe fentanyl, but it's not going to do anything for the xylazine and so we don't have a way of reversing that overdose. Besides potentially causing an overdose, for some reason this xylazine causes skin ulcers, potentially all over the body, even at sites where it hasn't been injected. And there are these really unsightly, very uncomfortable ulcers that can become infected and we've seen people with these terrible sores all over their bodies. And we also don't know for sure how to withdraw people from xylazine. If a patient is getting the xylazine inadvertently in the drugs that they're purchasing illicitly and then suddenly they come into treatment, how do we help them get off the xylazine without having terrible withdrawal symptoms? And people are starting to experiment with the alpha-2 adrenergic agonists like clonidine that are available to us to use for humans, but we still don't understand how well that works. So it's a big conundrum, a real problem, and it's just something we're going to have to cope with. Yeah, so some patients have had to have amputations because of these sores that get getting infected and gangrenous. So yeah, it's a really awful situation. Another one where, sorry to say, but the cartels are outsmarting us at every turn. So we're going to have to keep jumping in there and trying new things. Did that answer your questions about xylazine? Yeah, I'm just going to go back to, can you hear me? Yeah, I'm just going to go back to the question on acute withdrawals of when people are using both alcohol and opiates. And you suggested that we could use lorazepam, you know, in small doses, but sometimes it doesn't just suffice because most times, you know, the training is that you use longer actin benzodiazepines, the chlorodiazepam, diazepam in acute alcohol withdrawals. But when you're faced with a situation where, in this particular scenario, where you have to use lorazepam in the setting of both opiate and alcohol withdrawal, what do you do in that kind of situation? So his question was about, you know, using lorazepam short-acting versus, you know, more longer-acting benzodiazepine, like a diazepam or a chlorodiazepam side. And I will say that the literature actually supports the use of both, they have both the volumes and evidences for lorazepam and diazepam. We've seen, I've seen, you know, one complex case where, you know, a patient had a breakthrough withdrawal seizure on day six when he was on Ativan taper, lorazepam taper, when he went from 1 mg three times a day to 1 mg twice a day, and he had a breakthrough seizure in between. So we had to switch him to chlorodiazepam side, you know, for the better measure of withdrawal. So that can happen. The lorazepam, by far, I think a lot of inpatient units and outpatient settings, they have a lot of experience and comfort using lorazepam as the taper, the main agent. And the benefit of using lorazepam is that it can come in, you know, IM, it can come in PO, it can come in IV, it's quick, and especially if someone is, like, more older, more frail, I don't, I less worry about, like, snowing them. I less worry about their delirogenic risk when I'm using lorazepam. So in the same token, when I'm thinking about the fentanyl, have they used methadone or long-acting, you know, opioids, if I'm getting them on buprenorphine in a couple of days, I want to minimize the overall effects of sedating medications for them. My preference is that I use the lorazepam, and I'm going to evaluate their CY. If their CY is persistently elevated, if they have a history of a recent alcohol withdrawal seizure, I'm switching them to, like you said, Librium or Valium to make sure that I cover their alcohol withdrawal symptoms better. But if their CY scores are, you know, mostly below 10, they use, they require Ativan maybe once or twice a day, then actually that's my preferred agent. Yeah, and there's no right or wrong answer here. This is clinician preference and clinical experience. So I don't think D.C. is saying, this is the way you should do it. He's saying, that's what he does. Take that into consideration and make your own decisions. So I think we're right up at the lunchtime. So we're going to reconvene promptly at 1 o'clock. So if, I hope you're all savvy about where to get some food. I have no idea, but it's not easy to do quickly with 12,000 of us all descending on the restaurants at once. See what you can do. All right. Well, I think we'll start with the case and hopefully the rest of the crew will drift in after lunch and join us. This is the teacher. Robert is a 35 year old teacher who's thinking about his treatment options. He's been injecting heroin off and on since he was 16. He's never been arrested. He's been through many episodes of heroin detox, mostly outpatient methadone detox, but also been in three inpatient drug treatment programs. His last inpatient program was a 28 day drug-free recovery program, and he remained both heroin and alcohol free for about six months following treatment. So he had extended periods where he was doing well. He teaches math at a junior high school and is in some difficulty because he's calling in six too much. His wife is in recovery and insisted that he returned to treatment after she discovered that he was taking large quantities of codeine pills from several doctors for a back injury following an automobile accident. She is unaware that he is also injecting heroin at least once daily. He has been alcohol abstinent for the past two years. His only current medical problem is that he is hep C positive, and he has been so for at least 10 years. He states, doc, I know I'm an addict. My wife cleaned up when she was pregnant with our daughter and she has just got her 12 year chip. She moved on with her life, but I'm stuck. My back injury threw me into a tailspin. At first I really needed the codeine, but now I'm just using them to stave off heroin withdrawal. I really need your help. If my wife finds out that I'm back on the needle, she'll leave me this time. So this is the picture that is presented to you. A guy in many ways very functional, but in trouble with his opiate use again. So our questions, what is his diagnosis? Anyone want to take a stab at that? Can you get that? Someone wants to say it on the mic. Opiate use disorder. Thank you. Okay. Do you want to say very briefly what your criteria are for the diagnosis? Well, he's been using opiates or either heroin or this pain medication on a consistent basis. He identifies himself as having a problem with it, identifies an inability to stop using, and begins to question how, well, he begins to say that it's going to affect his marriage. So it certainly has had an impact on his life. Yeah. Multiple problems, multiple prior treatments. And so is there any question from anyone that this gentleman has an opiate use disorder? Okay. Well then let's talk about treatment. What do you think is the best treatment option for him? Anyone want to take a stab at how they would treat him? So we would try to first consider getting him off the pills that he's currently taking for a few days. Once he goes into a withdrawal, we could consider starting a low dose of Suboxone at that point. And probably offer him with some Clonidine there too, just to limit any symptoms. I'm having trouble hearing what you're saying. I'm saying that we can get him off the pills he's currently on and wait for the withdrawal to start. Once he hits a mild to moderate, then consider starting a low dose of Suboxone. We can also offer him with probably a low dose of Clonidine, just as a backup there too, to limit some of the other side effects that he could develop too. Okay. John, we realize it's hard for the person up there to hear because the speakers are facing that way. Okay. Okay. I don't know if you want to come down. No, I'll just stay put here. Any other comments about what they would do with him? Over here. Okay. Seems like a good candidate for Methadone. I'll repeat it for the recording purpose. I know everyone heard it. Okay. But he said it sounds like a good case for Methadone. Why would you suggest Methadone? Excuse me. Crime usage, he's tolerant, he's getting withdrawal symptoms, his wife is going to draw limits if she finds he's shooting up. It sounds like Methadone might save his, he's all of that, at least for a while. Well, what does the group think about Methadone versus Bup? All right. Let's see hands up for Methadone. Just a few people. Okay. Hands up for Bupenorphine. Okay. The only, I think clinically, I think they both would work. I think it's not clear that he's got an ongoing pain problem that he would need the codeine per se. If it were the case, it would be easier to supplement the Methadone if you were doing that. I think the one thing I would be concerned about is his job. I mean, if he is a school teacher, I think it would be easier to function being on Bupenorphine and easier to keep it quiet. I think if he was on Methadone, at least the way things are today, he'd be going to a Methadone clinic. And I suspect that would kill his job very quickly, you know, if the word ever got out. So that would make me concerned about the issue with the Methadone. But clinically, I think it's a reasonable choice. What would you do or how would you handle this if it turned out that he was positive for Fentanyl? If he was positive for Fentanyl, we could probably do two ways. The first way, we could wait for the withdrawal symptoms to first develop. The other way is that cross titration method that you guys were talking about earlier. Or we could start with like a Zubsolve and then swap over to Suboxone after three to four days and see how it comes along with it. Yeah, okay. Anyone else? Because if this teacher was in Boston, he might have thought he was using heroin, but my suspicion would be that his urines would be positive for Fentanyl, no matter what he thought he was taking. So that wouldn't be surprising to me. Anyone else would suggest they would treat him different way or manage it differently? Yeah, well, we don't find any heroin. It's unusual for us to have anyone test positive for heroin in Boston right now. You know, all of the urine tests that we get back for our patients are almost all fentanyl. Yeah, so it's just replaced that. And they may know they're getting it, they may not. They may think they're getting some other opiate. Yeah. So I, you know, I can tell you that our lab, we test for fentanyl. So if, you know, in my practice, if we are not testing for fentanyl, that urine specimen is useless to me. It doesn't really tell me anything, whether positive or negative. I imagine, so, you know, if you talk to like Quest or other lab, so, you know, her comment was that, yeah, you know, she's practicing in Chicago, Illinois, and her drug test doesn't contain fentanyl. So I won't say that I am not familiar with how the landscape of opioid use disorder in Illinois. So, but, you know, if you talk to like Quest or other lab, so, you know, her comment was that, yeah, you know, she's practicing in Chicago, Illinois, and her drug test doesn't contain fentanyl. Then you've got to talk to your hospital's lab. Because there are fentanyl immunized in their fentanyl G-similes testing available. So, I fully agree, so, her comment was that, yeah, you know, with the limited research, the hospital is going to buy back about ordering extra tests for fentanyl. And if you feel like you need to test for fentanyl, then you've got to talk to your hospital's lab provider. Because there are fentanyl immunized in their fentanyl G-similes testing available. To advocate to the hospital, like, we've got to, you know, we've got to have availability for fentanyl testing. Two different panels, one is a six-drug panel. The other one is almost 16 or 20-drug panel. Because if you have a strong suspicion of fentanyl usage, you can use the 16 or 20-drug panel so that it covers a whole slew of drugs that people can potentially use. And her, you know, comment also, thank you for your comment, her comment was that, you know, so, sure, like, we've got to buy fentanyl tests, but what should I do right now in this practical scenario where I don't have the fentanyl tests available? So, I fully agree, so her comment was that, you know, with the research the hospital's going to fight back about ordering extra tests for fentanyl. And because fentanyl, you know, opioid epidemic is, you know, all over the country from all the, you know, global. Now, my suggestion would be that, you know, you'll talk more about the drug screen tests later on, you know, today, but, you know, it serves a little bit of different purpose, but if you're trusting the patient and he really doesn't have any reason to lie to you about, you know, faking opioid use disorder, because he feels like he gets caught by his wife, then he's, you know, like, his wife will leave him. Sure, you have to think about the diversion risk for buprenorphine if someone come and they just fake about their opioid withdrawal symptoms. There are better and easier ways to make money. He can easily deal part of the fentanyl that he gets to make the, because I suspect, as a schoolteacher, he cannot afford to use, you know, opioids every day. So, there are, you know, just realizing that there are easier and better ways to make money than to lie to me at the risk of being caught by his wife. Thank you for your comment. Her comment was that, you know, so, sure, like, if he's not faking symptoms and adverse diversion for fentanyl test, but what should I do right now in this practical scenario where I don't have the fentanyl test available? You said, did I state it right? So, then you just have to follow the clinical, you know, information that you get from the patient and you also are gonna have to treat him with buprenorphine. Now, when I talked about how the test might be useless to me without fentanyl, that's more on the maintenance phase, whether I'm trying to evaluate whether he's doing well or not. And if those tests are not tested for fentanyl, he really doesn't have any reason to lie to you about faking opioid methadone because if he gets caught by his wife, then he's, you know, like, his wife will leave him. And then I have to just rely on patient's diversion risk and just maybe ask someone to come and they just fake about their opioid withdrawal symptoms. I would just make one added comment is that I think we're entering an era where the cartels and the chemists are going to keep finding things that we don't know about now. And I think to practice good state-of-the-art medicine, you're gonna need quality testing and that's gonna have to be done. You may have to raise that as political issues to force the insurance companies to pay for it because you're not gonna be able to practice good medicine if you can't do those tests. So, at least if you're reasonably assured that he's not faking his symptoms for diversion purpose... Now, I'm gonna shift gears to the next talk. This is all about counseling. You're fairly confident that he has opioid use disorder, then you can start... I want to talk about the impact that counseling has on recovery. What is evidence-based practice? And what the practical clinical models are, which counseling has really been demonstrated to be more effective in the opioid use problem under the condition. So, we'll talk about 12-step facilitation, cognitive behavior therapy. We'll go into more details about motivational enhancement therapy. Just a little background information. This slide just demonstrates that adding good counseling will improve your outcome. This is a study done by David Filene. I would just make one added comment is that I think we're entering an era where the cartels and the chemists are gonna keep finding things that we don't know about now. And I think to practice good state-of-the-art medicine, you're gonna need quality testing, and that's gonna have to be done. And you may have to raise that as political issues that force the insurance companies to pay for it because you're not gonna be able to practice good medicine if you can't do those tests. So, okay, well, let's move on here. Now, we're gonna shift gears for the next talk. This is all about counseling. This was looking, again, at methadone clinics, but I think the point is certainly true for the total population. I wanna talk about the impact that counseling has on recovery. What is evidence-based practice? And what would happen with models are for which counseling has really been demonstrated to be more effective with people with opiates problems or other addiction problems, as we'll talk about, and the 12-step facilitation, cognitive behavior therapy, and go into more details about motivational enhancements. Trained psychologists, trained social workers, psychiatrists, you can see that you've got more, this slide just demonstrates that adding good counseling will improve your outcome. This was a study done by David Feilene. You can see here that he was comparing brief counseling to brief counseling, psychiatric problems, plus other medication, and you're looking at the percentage of opiate-positive urines, and you can see that the enhanced counseling got better results than just the brief counseling. Brief counseling, in the description, there was probably just exotic staff in the methadone clinic who were not really sophisticated, and compared to what results you would expect if you had trained social workers or some medications. Things that are listed, this is a study done by McClellan, and on this slide are things that actually made the outcome worse, not better, but worse. It's the efficacy of the psychosocial counseling. This slide was indeterminate evidence of effectiveness. The things that you're seeing on this slide didn't make it worse, but they didn't make anything better, were not very well trained. Standard electrical-version, non-behavioral marital therapy, I would caution you that marital therapy is very helpful, but it has to be the right kind of marital therapy. There are different ways people can get it. We won't go into that in more detail, but non-behavioral marital therapy wasn't helpful. And it turns out that just plain stress management with a higher degree of counseling, and this, when they looked at the number of people in the population who got hospitalized, none of the patients who were on enhanced counseling or medications that really have strong evidence for being effective. Of brief interventions or frames, we'll talk about that in a second, motivational enhancement, cognitive therapy, 12-step facilitation, self-control, the counseling will have an impact on the outcome of treatment and the medications that are listed. So all of these slides describe three sets of counseling techniques. This first slide here talks about 12-step facilitation. This project match was a large study. It had some modifications. Modes of psychological intervention, and it was all done by manualized therapy, and here the modes were manuals for 12-step facilitation. It was not AA or NA, but it really helped patients get to AA or NA. It was 12 steps, the focus on resolving the evidence of effectiveness. The things that you're seeing on this slide didn't make it worse, but they didn't make anything better. But this is what, so electrical aversion, non-behavioral marital therapy, I would caution you that marital therapy is a very helpful, but has to be the right kind of marital therapy, and there are different ways of doing it. We won't go into that in more detail, but non-behavioral marital therapy was helpful, and it turns out that just high stress management wasn't particularly helpful. And that means, in a sense, that a very borderline, these are the evidence-based practice, these are the ones that groups like AA or NA, people had to be comfortable with groups and it helped if they really have strong evidence for being effective. But the data also shows that the most powerful influence is actually just that group membership, cognitive therapy, 12-step facilitation, self-connect the patient with groups that they're gonna feel comfortable with. So you may need to match them by age, race, gender, sexual orientation, social class. All of these things will determine how effective your patient is able to facilitate. This project match was a large study. There was just loads of psychological intervention and it was all done by manualized therapy. You wanna match them to a group that's similar to a manual for 12-step facilitation. It was not AA or NA, but it really helped patients get to AA and NA. It always helps that you suggest that you go to several groups before you decide whether it's gonna work. It's really helping them try to find a group that is a better match for them. This is what, if you talk to them afterwards, you wanna process the group experience, work through their resistance. What that showed was among other things, the best candidate for support in self-help groups is get off your medication. You're not in real recovery nature. Men, psychologically healthy with weak ties to family. All of that is not accepted by the organization, certainly not AA policy. Patients with schizophrenia did not do very well with groups like AA or NA. People had to be comfortable with groups that helped them recover. But the data also shows that the most powerful influence is actually just group membership, things like Smart Recovery or AA versus NA. It doesn't matter if you just find a group that's functional, it may help the patient find it. You may need to match them by age, race, gender, sexual orientation, social class. All of these things will determine how effective a role model or mentor is able or how important it is for the patient to blend with the group. Now this just walks you through how you might sort of make that type of referral. You wanna match them to a group that's similar to their demographics. It helps if you can find someone with a minimum of first group. It always helps that you suggest they go to several groups now or they decide whether it's gonna work. It was also an option, really helping them try to find a group that is a better match for them. So if you talk to them afterward, you wanna process the group experience, work through their resistance. This was for 12 seconds, correct misinformation. Because one of the things you may hear in self-help groups is get off your medication, you're not in real recovery. Learning model, if you will. They need to learn how to, all of that is not accepted by the organization, and certainly not AA policy. Look specifically for people who had just substance use problem, in this case alcohol problem, but they may not hear that from the average number of their diagnoses. So you need to correct that. However, there is a form of cognitive immediate therapy called seeking safety. How many people here know what seeking safety is? It doesn't matter if you just find a group that's functional, but it's a specialized form of CBT. So think about this, you wanna help them find a sponsor. If people have been trained to do it, and people can learn how to do it, there's a manualized group therapy. So you have to find a sponsor who is comfortable with their being on buprenorphine, or their being on methadone, or naltrexone. So it's really designed for a dual diagnosis patient. It focuses on safety, that is, no more substance use and no acting out. They should look for someone who combines cognitive behavioral approaches for both disorders. And we've found since that it's useful, not just for PTSD, for their whole range of other psychiatric conditions, and there was a manual for that, with the seeking safety protocol. NIDA and NIAAA have these manuals, manualized folks, and again, there's a manual, 12 sessions, builds cognitive behavioral skills, sees drinking as a functional problem related to skilled diagnosis. So it's a learning model, if you will. They need to learn how to stay sober. It's not designed for, it spends some time talking about motivational enhancement therapy, who had just substance use problems in a case-alcohol problem originally, that is, and not other psychiatric diagnoses. People make changes in their life all the time, and there are fairly consistent patterns that go through when people make a change. To give one very simple example, if you all decided to come to AA, or come to CBT, the psychiatry mediation, so how did that happen? If people in the beginning you considered the idea, you thought of it as a manualized group therapy, do I really wanna go to APA this year or not? PTSD and substance abuse treatment. So it's really designed for a dual diagnosis patient. It focuses on safety, that is, no more substance use and no acting out. It combines cognitive behavioral approaches for both disorders, and we found that it's useful not just for PTSD, but there are a whole range of other psychiatric conditions. If you determine what you have to do, then you put them in place, and eventually you get to action where you get here today. So you went through a sort of modified process of change, behavior therapy, well, people have said, well, this applies to those cognitive skills. It's not about giving up substance abuse as an example of changes in your life, stages of change theory explains the process. I spent some time talking about motivational enhancement therapy, and it basically means people move step by step through a fairly predictable set of stages, and your job as a therapist is really to understand where they are in that process and then help them through the next step, when people make a change, not to cure, not to resolve, not to jump three steps ahead. To give one very simple example, when you all decided to come to AA, or to come to the psychiatry meeting this year, the stage of change begins with pre-contemplation. You don't even know you have a problem. You thought about it. So this is the heroin outage or the alcohol, or the individual who's just happy with their drug use, their substance use, has caused problems, they can still afford it, they haven't gotten into any trouble, so they're just enjoying it. Good, so they're pre-contemplators, but suddenly things begin to catch up with them, well how do I get there? They move into a contemplation state, where they're now aware that something's wrong. Once you've figured out what's right and what's wrong, what's going on in my life, and you move into determination where you have to make a decision, action where you get here today. So you went through a sort of modified process of thinking about it to make your decision to change. And then you have to figure out, well how am I gonna make that change happen? What do I have to do? That's an example of changes. And you have to go through that period to make change decisions. Then you reach action, where you actually implement the changes, and you make it happen. That's the action, and then that's followed by maintenance. And maintenance is a fairly predictable set of stages. I think we all, your job as a therapist, I wanted to understand where they are in this process, and I got to the point where I actually started practicing, and playing tennis, and not to resolve, not to jump, become a good tennis player, but go slowly one step at a time. How do I become a good person in recovery? How do I make the recovery work? How do I make it last? How do I get through particularly difficult problems? You don't even know you have a problem. There's a lot you have to learn to make the maintenance successful, and all of this has been described in great detail by the work of Francesca D'Inclementi. They haven't gotten into any trouble, so they're just enjoying it. But let's go back through some of this stuff. But suddenly things begin to catch up with them, and they move into the contemplation stage, where they're now aware that something's wrong. Interview them, find out, they're beginning to think and understand they've got a problem. I'm sure we've all seen patients with substance abuse problems where their boss has forced them into you, their spouse has forced them into you, and they say there's no problem. So you've gone from just thinking about it to making the decision to change, and then you have to figure out, well, how am I gonna make that change happen? What do I have to do? That's the preparation. And you have to go through that period to make these decisions. What works for people who are in denial is not the same thing that's gonna work for people who are in maintenance who make it happen. That's the action. And then that's followed by maintenance. And maintenance is the fine-tuning of this. I think we all, I decided I wanted to play tennis, but I went through this process, I got to this point where I actually started with pure style playing tennis. And then I get into maintenance. How do I become a good tennis player? It's just like, how do I become a good person in recovery? We were taught things like, motivation is something inherent in the patient, and we can't treat you until you're motivated. And if we ran into somebody who wasn't motivated to make the maintenance successful, all of this has been described in great detail by the worker at Prochaska and Dill. That was a routine way of dealing with the addiction problem when I was doing some of this stuff. And what this says here, well, you can work with people who are ambivalent. First of all, you want to identify where the patient is and it's your behavior that will matter in terms of helping them. I'm sure we've all seen patients with substance abuse problems where their bosses force them into you, their spouses force them into you, and I suspect all of you have had experiences like I've had where you maybe were working in an emergency room and you saw some other doctor, and you know that 10 minutes after talking to anybody, that doctor had the patient eating out of their hand. You're helping them along. They were very comfortable. And then this other doctor here, 10 minutes after dialing is not the same thing that's going to work for him. He had a marvelous tendency to make people upset. And their goal is really just move the patient relatively slowly one step at a time instead of looking at the fact that maybe the basic concepts here, and this part is really important, that your style determines resistance and change. And it should be our responsibility to work with unmotivated people and learn how to talk to them, learn how to ask questions without getting in the way of the patient. Learn to out-treat you until you're motivated. And if we ran into somebody who wasn't motivated for care, we would tell them to go away and come back in six months or a year when you're ready. that was a routine way of dealing with the patient-patient problems when I was a resident. It really is a goal, not a style. You want to get them to the point where they have confronted their issues, but you don't want to confront them that will matter in terms of helping them get through this. So that your style can either make them more resistant or can make them progress. And I suspect all of you have had experiences like I've had where you maybe were working in an emergency room and you saw some other doctor and you know that 10 minutes after talking to anybody, that doctor had the patient eating out of their hand. They're helping them along, they're very comfortable. And then this other doctor here, 10 minutes after talking to the patient, he's furious and fighting with them. I mean, he had a marvelous tendency to make people have increased motivation and reduce resistance. And motivation is going to emerge out of the relationship with the patient and the therapist. Push the wrong buttons. And I think you all have some concept and recognize that it's part of our job. It should be our responsibility to work with motivated people and learn how to talk to them. Learn how to ask questions without getting them angry. And I think that's a very important part of recovery. Learning how to ask questions without getting more denial. Learn to ask questions so that when they enter recovery, they are defeated. They are depressed, they feel hopeless. They have to understand that confrontation would really lose the skills that you can lend to the problem. It really is a goal, not a style. So it's part of, it should be part of our arsenal to know how to do that and to lend those skills to the patient so that they can make progress. So what are the concepts here? First of all, ambivalence is normal. That if you are confronted to it, you will probably have bad results. I'm ambivalent every time I have to pay a bill. I would like to keep the money, but I can't do that. You never win arguments with patients. And with substances, I think get into it. You all recognize people wouldn't do this. They're not crazy. Resistance is what keeps change from happening. Or at least they have fond memories of what heroin used to do for them or what alcohol used to do for them. Or how wonderful it was to be drunk and they forget the next 10 hours that happened afterwards. But they have something there that they are enamored with that they're trying to catch up with again and recreate. So there's some positive gain in their substance use. And you have to help the patients resolve the situation. But whatever that positive gain is, it's not too expensive. It's no longer safe because a lot of the patients, when they enter recovery, are getting to the point that they think they're gonna get to. They're hopeless, they're getting somewhere worse. And if you talk to some patients, you get from them this notion that they have this fond memory the first time they got high. Or they remember the first time they drank. Well, most of the people I talk to say, oh, I'm not an alcoholic. I couldn't tell you what I had my first night. But if I ask a lot of my patients, do you remember the first time you got drunk? They will tell you in fond detail what that was like and where it was when it happened. First of all, ambivalence is normal. We are all ambivalent. I'm ambivalent every time I have to pay a bill. I would like to keep the money, but I can't do that kind of thing. It's just a normal part of living. And even though things are bad now, they tend to plot all that out. But if you can help them resolve the ambivalence, I think you can help the patient. So what are the techniques that you have to treat them with respect? You have to develop the skeptics. Or how wonderful it was to be drunk. Gently point out to them the next 10 hours between what they want and what they got. But they have something where they're enamored with that they're trying to catch up with again and recreate. So there's some positive gain in their substance use. Then you have to help the patients resolve the role with the resistance. But whatever that positive gain is, it's not too expensive. Don't let it roll over you and flatten you. Instead of getting to the point that they think they're going to get to, they're getting somewhere worse. And if you talk to some patients, you'll get from there the social mix. They have this fond memory of the first time they got high. Or they remember the first time they drank. But if they've done a little bit, I couldn't tell you what I had my first drink. Well, that may be a victory. But if I ask a lot of my patients if they remember the first time they drank, they will tell you in fond detail what that was like and where it was and what it was like. And you can reinforce the message that this is possible and that you are not hopeless. So anything that you see going on, they may spend their life trying to recreate that experience to help them rebuild self-esteem. And that's what drives this to continue. Even though things are bad now, they tend to blot all that. Now, I'm going to just walk through this process in a little bit more detail. So we're starting with someone who's in pre-conflict. So what are the techniques? And you want to get to the point where you're making them nervous. Gently point out to them the difference between what they want and what they got. Or where they're going in a variety of ways. One of which is simply giving them feedback and by avoiding to the cage. If you run into resistance, they use the, this isn't normal. 10 drinks every night is not normal drinking. Bounce with it. No, that's not what normal people do. Don't let it roll over you and flatten you. You've got to sort of bounce around and compare these results to what's normal. And be careful, whenever you see sparks on a weekend night, three beers, support their self-efficacy. Ten beers? Remind them that they're not helpless. They may have globalized how bad. One of the things that you find, if they've done a little bit, if they got to your office on time, well, that may be a victory. They trade their friends for people who are like you. They get to a point where only the people they know well are people who do reinforce. And you can reinforce the message. You don't get invited back to your spouse's parents' house if you come in and throw up on the table and there's something that doesn't endure you to help them rebuild social networking and give them hope. And you have to look for, over time, you extrude the people from your group who don't approve or don't act like you do. And then it becomes easier to deny that what you're doing is a problem. Because everybody around you is doing the same thing. Everything is wonderful. And you want to get them to see these things. You want to summarize these conclusions that you're trying to point out to them. But you never want to argue. But you do want to let them know they're not hopeless. And one of which is simply giving them feedback. Lab results. Do the cage. Get blood alcohol levels. But what about the people who are extremely resistant? This isn't normal. 10 drinks every night is not, it's helpful, I think, in situations like that to build a relationship. So your goal in the beginning is not to cure and not to get them to stop drinking or drugging or whatever. Maybe two beers on a weekend night. Three beers. To get them comfortable with you. But 10 beers? And have a relationship with you. No. And sometimes it's like the person who comes in who you know the problem is because they're drinking and their spouse is ready to leave because of the drinking. They don't want to talk about the drinking. But maybe they want to talk about why they have conflict with their spouse. Maybe there's some area there that will get them to come back to the office. You don't get invited back to your spouse's parents' house if you come in and throw up on the table. And you want to use sort of client-centered activities. What is important to them? What are they concerned about? But you don't need to get into behavioral things. You don't want to get in their group who don't approve or don't act like you do. Just keep it simple. And then it becomes easier to deny what you're doing is a problem. Is there anything that they're unhappiest about? And you've got to help them see these things. You want to summarize these conclusions. Let you know that your girlfriend is angry because she's drunk on the table. Let them know they're not acceptable and give an explanation of what's going on. But maybe they're willing to talk about why this girlfriend is so difficult. This is an open-ended question. And you can use that to build your relationship. It's helpful, I think, in a situation like that to build a relationship. If your goal in the beginning is not to cure them, not to get them to stop drinking or drugging or whatever, but your goal is really just to begin to get them comfortable and have a relationship with you. And sometimes it's like the person who comes in and there's something they're interested in. But maybe the reason their girlfriend is upset all the time has to do with what they're doing. It's not because she's a bad person. Maybe there's some area there that will get them to come back to the office. Once you get them to the point where they recognize that you can use that as a way to build a relationship. So how do you get some client-centered activities? What is important to them? What are they concerned about? What are they wishing? What are they hoping for? You don't always start with what's positive. What do they like about their substance use? What is it they're concerned about? Is there anything that they're unhappy with about? And you make them uncomfortable. And I'll blame it on other people for them. And they will not let you know the thing. Their girlfriend is angry because he's drunk all the time. But nobody wants to know what the good things are. But that's a good way to start this discussion is get them to articulate what is so difficult. And after they've made that case, then you can begin to ask questions like, do you ever doubt this? Is there another side to this? Are there some things we haven't talked about? So it's like your supervisor, whereas the goal is that over time, the patient begins to trust you. You don't start out by telling them they're screwed up. They don't know what the heck they're doing. What you start out by telling them all the things they're doing well and the connection between what they've defined as a problem and the fact that they're substance use. You may begin to start raising the pringles that their girlfriend is upset all the time. But you're doing that from a position of strength, not because she's a bad person. You don't start with the negative. Maybe they can begin to connect the dots. And then you move to the negative. Ultimately, once you get them to the point where they recognize it's a problem, the next step is determination. So how do you get someone from determination? But you want to help them talk about their guilt and their fantasies. What are their wishes? What do they hope for? What they're doing. And one of the things you're going to run into with a lot of patients is the first step in this process is not recovery. It's pulling them back. It's not, oh, I'll never drink again. Because I guarantee you it doesn't work. And very few people ask that. Well, I want to be normal. And what that means in their group is it's normal to drink 10 beers a night. Maybe it's normal to drink three beers a night. But normal isn't not drinking. And after they've got case, then you can begin to ask questions like, well, do you ever doubt this? Is there another side to this? Or is there some things we haven't talked about? Not every day. I didn't want to give it up. I don't want to give it up. But I want controlled juice. So in our society, for them, controlled juice is what they're doing. You may start out by telling them all the things they're doing well on that question. And that may be where you start therapy. And then after you've built a relationship with telling them what they do well, you may begin to start raising the pringles that they don't be a normal part of the process. But you're doing that from a position of strength and a position of trust. You don't start with the negative. You begin with the positive. And then you begin to think, well, how do I achieve controlled drinking? Ultimately, you want to help them. And we talked about that prior before. Well, how do I achieve using heroin conflict two days a week instead of seven days a week? But you want to help them talk about their guilt and their anger. But you may have to say, well, let's try what you're suggesting and keep records. And one of the things you're going to run into with a lot of patients is the first step in this process is not recovery. If you want to just, it's not, oh, I never drink again. Or I never want to use heroin again or whatever. The first step is always, well, I want to be normal. And what that means in their group is it's normal to drink 10 beers a night. Maybe it's normal to only drink three beers a night. But normal isn't not drinking. So that they often, what they want to do is use heroin like they used it when they were 17. Just on occasional weekends or when they had extra money. Not every day. Then I think they may want to get into formal addiction treatment. So in our society, your choice of referral or your choice of techniques that you're going to present to them will depend on what their goals are and what action means to them. And that may be where you start therapy. Because action to them may not mean the same thing to you. And you have to understand that that may be a normal part of the process. So moving from determination to action. You're aiming at getting to the point where they want to do something. And maybe the do something is only, OK, well, how do I achieve controlled drinking? Or how do I achieve explore options? We talked about that a little bit before. How do I achieve using heroin is to develop a man instead of seven days a week. And the reason you want to do that is you want the patient to have a sense of choice. So you may spell out four or five different ways you can achieve recovery. See how you do. See, if this is your goal, let's see how well that works. You want to explore it. If you want to just, if you're really feeling like they have some autonomy and that you're respecting their wishes, you may need more counseling therapy. And I think it's more important if they just want to control it, they may not be ready to be referred to a substance abuse treatment program. Because I think they're much more likely to really invest in it or continue the choice to do it. You may not be the perfect answer. But if they've owned the choice, I think you have a better chance of that. If they decide they really want to stop something, then I think they may be ready to get into formal addiction treatment. So your choice of referral or your choice of techniques that you're going to present to them will depend on what the goals are and what action means to them. Because action to them may not be the same thing that action means to you. And you have to understand how to achieve that. And you have to understand how to stop drinking coal. Do you want to stop drinking coal or drugging? Or do you want to just stop using on the weekends? Do you want to use half as much a day as you use now? You have to think about the treatment plan, the hospital, your options. One of the tricks in getting them to start treatment is to develop a menu. But you need to understand what the patient is going to think about. And we're going to have a sense of choice. So you may spell out four or five different ways you can achieve recovery. I have plenty of opiate use patients who go to AA and much prefer AA to AA. I have several patients who go to NIN thrive. So they're feeling like they have some autonomy and that you're respecting their wishes. And I think it's more important that their self-therapy family therapy is an ideal world and that they have family therapy for everybody. Because I think they're much more likely to really invest and get a spouse in if they've made the choices to do it. They may not have spoken to their parents for five years. But if they've owned the choice, I think you have a better chance of that. But whatever you do, it's important that you support whatever choice they make. That you try to achieve things that are possible. But in that process, you want to really start negotiating treatment options. And what are the choices we're going to look at for someone who's just starting recovery to help them feel better about themselves? Talk about either a detox or talk about a gradual taper. But sooner or later, if you're working well and this is going well, you get to action. We get to treat you half as much a day as you use now. And I like to think about tapering particularly as a treatment platform. And I think you've heard today, it is probably the most powerful part of the recovery. Some of them may not work. Probably better data for that than any other counseling or anything else. But I still think of it as a term, as a platform. And by that, I mean it may make possible to do other things. If they've got their life back under control and they're on medications with methadone and buprenorphine or what have you. So it may now be possible for them to take buprenorphine. It may be possible for them to do other things. We've got individual therapy, group therapy, family therapy. In an ideal world, we would love family therapy for everybody. So it may be possible for you to. You may not get a spouse in. You may not have supported your parents in five years in a 12-step program. So that isn't a realistic option for a patient. But whatever you do, I think there's no question in my mind that people will do better. And it will be easier for them, particularly in the first couple of years. If they're involved in a recovery group, and they come back and say, I really would have made some progress. And that you can reinforce that. And I think you have to avoid passive analytic approaches. They don't want to think about it. But sooner or later, if you're working well and this is going well, you get to actually resolving certain kind of treatment strategies. And it may be very helpful for some patients. And I like to think about buprenorphine, but there's absolutely no data, the psychoanalysis going. As I think you've heard today, it is probably the most powerful part of their recovery. It just isn't a technique that is useful to do that. It does lots of things, but it doesn't do that. Than any other counseling or anything else. So uncovering therapies when someone has a term as a platform is not really good. By that, I mean it may make it possible that they'll do what they always do, which is go out and get drunk, or get intoxicated. So if you're stirring up in their background with methadone or buprenorphine or whatever, it may now be possible for them to conclude that it may be possible for them to do other things. There are special techniques for working with people who may not speak to them again. They may be willing to get involved. And we certainly recommend integrated therapy. But sometimes that needs to be done in residential programs. It needs to be done in intensive daycare programs. It may be very difficult to explore someone's trauma and then tell them to go home and come back a week later. That may not be feasible. It may not be possible. So you've got to use your head in how you're doing it. And the other just overall point is that recovery for any one patient is a trial and error process. You cannot predict ahead of time what is going to work or what they will need. You may not know until two years later that every time Uncle Fred comes to town to visit, we go out and get high. Or that Uncle Fred is going to arrive with some wonderful dope and he's going to push you really hard to use it. You may never have heard about Uncle Fred. But there may be particular situations and environments, if you will, that are problematic for your patient. And you're going to have to work with identifying them, finding alternatives, and building that A, B, E, which is causing more trouble than you're helping. So when they're doing well and they're coming along, you're going to have, there are special techniques for getting along with that. Absolutely, positively, you can predict. I think maybe, and we certainly recommend integrated therapy, but sometimes that needs to be done in a residential program. It needs to be done in an intensive daycare program. It may be very, very difficult to explore someone's trauma and then tell them to go home and come back over this way. And it's very important that you translate those events in a very particular way. The first thing is that you have to go and get them back in recovery as soon as possible. They have to know that they can come back and see you, that you cannot be angry, you will not throw them out that they are welcome, but it's all right to come back and say, I screwed up. And I can tell you that you can tell them that every time Uncle Fred comes to town to visit you and know that it is real. Or that Uncle Fred is gonna arrive with some wonderful dope and he's gonna push you really hard to use it. And I think you may never have heard about Uncle Fred. It should be a learning opportunity. But there may be particular situations that your environment's issues that are problematic for your patient, and you're gonna have to work with identifying them, finding alternatives. Just think about, if you had a five year old at home and you just got them their first bike and they went around the corner too fast and they're coming along, you're gonna have relapses. You're absolutely positively, you're never gonna learn. I think maybe you would know that you pick the kid up, you put him back on the bike, and tell him don't go so fast. Maybe one or two patients who've recovered and been fine. These things happen once, and they never had another problem. This is how you can avoid the problems in the future. Everybody else keeps slipping and falling and getting into trouble. It's not a sign of perpetual failure. And it's very important that you translate how to take these episodes of relapse in a very particular way. The first thing is that you have to go and get them back in recovery as soon as possible. They have to know that they can come back and see you, that you will not be angry, and may help you redefine your goals, that it's all right to come back and say, I screwed up, where their difficulties are, where their strengths are. And I can tell you that you can tell them that, and they may be able to intensify treatment back to them as a result of a relapse. But once they get to know you and know that it is real, the answer may be not that the treatment worked worthless in their capacity to use you as a therapist. Maybe you need a group. Maybe you need to go to AA every day instead of once a month. It should be a learning opportunity. A relapse is not a symbol of failure. And it's not a confirmation of their underlying idea that they're hopeless and they can never get none. Just think about, if you had a five-year-old at home and you just got them their first bite, and they went around the corner too fast and fell off, you wouldn't have to deal with how you negotiate addiction treatment with somebody who has other problems. You would know that you picked the kid up, you put him back on the bike, and you tell him, don't go so fast. There are other things you're concerned about. Well, first of all, sobriety has to be the point of problems in the future. And the reason I say that is that if you can't keep them sober, probably everything else you're trying to do will fail. Their depression treatment will probably fail. It may be very helpful for identifying skills that are both strong and skills that are not strong. I think you can't forget that sobriety has to occur. And it may help you redefine your goals for the patient. If you can learn where their difficulties are, where their strengths are, then you may be able to intensify treatment activities as a result of relapse. The answer may be not that they have to learn how to be hopeless, but to learn how to find the right group. They have to learn how to use the techniques of AA. Maybe you need to go to AA every day instead of once a month. But it may not become as simple as they have to learn how to. There are ways to do this that really work. Relapse prevention may be helpful when relapsing occurs. And you can see this when relapse solves problems. But to my mind, it means, as I mentioned before, that relapse is a learning episode, not a phase. And this is a generic kind of statement. And while you're doing all this, avoid excessive dependency. Particularly a psychiatrist has to deal with how you negotiate addiction treatment with somebody who has other problems. You're also managing their depression, their PTSD, their anxiety disorder. There are other things you're concerned about. Don't become their respite. That's become the primary goal. Because the reason I say that is that if you can't keep them sober, probably everything else you're trying to do will fail. Their depression treatment will probably fail. Their PTSD will probably get worse. But if you want to make progress with any of these other conditions, I think you can't forget the sobriety has to occur. And it looks like the things, structure therapy, CBT, 12-step facilitation, motivational enhancement therapy, these kind of structured therapies are the best techniques that we have to help people get sober. They have to learn how to join AA. They have to learn how to find the right group. They have to learn how to use the techniques that they have because they will be very helpful to them. But it may not become simple. And by what I mean there is we're not just talking about someone you see once a month who spends five minutes with you and writes your name on a prescription and hands it to you. That's not medical management. Relapse is a learning process. It's probably what you're doing naturally with most of your patients like this. You may be seeing them to refill their prescription for buprenorphine. The way you do that is just make sure that they're dependent on other people too. You're getting some results to find out what's happening in their life. Are they going to groups? Are they getting along with people? What are the problems? What are the successes? You want to make sure they understand the recovery techniques, understand their disease. You want to encourage them to keep going. You want to encourage them not to use. You want to encourage them to stop marijuana. You want to encourage them not to use a little cocaine as a way to handle these difficulties. You want to broaden the concepts of what recovery can mean for them. You want to reinforce they're going to AA or NA. And just reinforce the lifestyle changes that are going to do this. And you know once you get good at this, once they're relatively stable, you can do this pretty well in a half an hour visit. This is shifting gears, but it's talking about using the patient. Using the prescriber as a source of other kinds of therapy for an addiction patient. You can do that. Now this particular mode of treatment, which is a bare bones intervention, has been codified by the VA and it's been researched. That's not medical management. It's probably what you're doing naturally with most of your patients like this. You may be seeing them refill their prescriptions from NIDA, where they have looked at this model. How are you doing? What's going on? Checking your urine. You're getting some results. And one of the things that the NIDA trials have shown is that this is particularly useful for patients who don't have really severe psychiatric problems. You want to make sure they understand people who've never used needles. Recovery techniques understand their disease. People who got in trouble, but mainly through snorting or sniffing or whatever. You want to encourage them to keep going. You want to encourage them not to use. You want to encourage them to stop marijuana. You want to encourage them to go out and use a little cocaine if they know how to do. You want to broaden the concepts of what a skilled therapist can do with minimal visits. You want to reinforce that you can't do this with patients with severe problems. And just reinforce that lifestyle to put healthier patients and you will see that this is a way that they can be managed. You can do this pretty well in a half an hour visit. So just to sum up some of this stuff, you don't have to spend a couple hours a month with a lot of these patients. As long as you guarantee that any of the patients that get in your office with an opiate use problem, if you're a psychiatrist, the odds are they've got three other diagnoses, but there's some other psychomorbidity that's there. You want to make sure that if they're getting an individual therapist, that they've got skilled VA therapists. The guidelines describe how to do this with substance abuse patients. And I think specifically mentioned the long term therapy is probably more effective than high intensity short term therapy. Where they were researching medication. The recovery program that charges $50,000 for a month as shown is the funds may have great food, may be in a beautiful location, but there's no evidence it works. And going to a not so fancy clinic with people who've never used may be much more effective. They've got in trouble, but mainly through snorting or sniffing, so they're not the most severe addicts. It doesn't force them to go to groups. It doesn't force them to go to individual therapy that they don't want to do. It's a bare bones way of doing it that a skilled therapist can do with minimal visits. But you can't do this with patients with severe problems. They require more intensive care. Some of the best recovery physicians who are in recovery. Well, what's different about this? They've got the board of medicine leaning over their shoulder. They've got somebody checking their urons all the time. They've got somebody forcing them to go into recovery activities. People do very well if they've got an enlightened court, not a court that throws them in jail, but a court that forces them to go to treatment. If you're a psychiatrist, the odds are they've got three other diagnoses. And gives them feedback. That there's some other supports to their recovery. So external supports can be very helpful if you're using them to keep the patient in treatment. Because the difference between someone in that program and someone else, if someone else starts drinking, get in trouble, they run away in therapy, you may not see them for three years. Probably more effective if someone who's got the court breathing over their shoulder, maybe back a week from now. So the recovery program that charges $50,000 for a month and forcing people to stay with food, maybe in a beautiful location, but there's no evidence it works. So these are some recoveries. And going to lots of fancy clinics once a month may be much more effective if they do that for the next five years. That may be a much better way for them to spend their money. Well, we've got time for one or two questions. You want to integrate their self-help programs with the medication and with family therapy, if you could do that. As I said before, try to get them back in therapy quickly if there's no relapse. I think I said confusing to you or anyone want to get into an argument with me? I disagree. Best recovery come from physicians who are in recovery. Well, what's different about them? Well, they've got the Board of Medicine leaning over their shoulder. Okay, well, we'll have time later this afternoon if you have questions come to you later on, we'll be glad to do that. We've got somebody forcing them to go into recovery activities. So we'll be talking about psychiatric comorbidities and pain management. I know a lot of our patients have pain as a comorbid medical condition. Some of them may have started using opioids as part of a chronic opioid therapy, and they developed opioid use on top of that. Some of them have developed pain after developing opioid use disorder, and it's just that may be bothering them, and they may be confused with the triggers for them, so hopefully we'll be addressing some of the questions about that. Someone who's got the cord breathing over their shoulder, maybe that's what we could do now. And I think that quick return to treatment and forcing people to stay with treatment long term is very helpful. So these are some recoveries, and I'm going to stop at this point. How's my time right now, Andy? I don't know why. What? Okay, well, we've got time for one or two questions. Anybody? So as you can see, the mental illness and substance use disorders in the United States, they have a lot of overlap. Anything I said confusing to you, or anyone want to get into an argument with me? Substance use disorder and mental illness. And in 2019, 60 million Americans have mental illness and substance use disorder. Okay, well, we'll have time later this afternoon if you have questions come to you later on, we'll be glad to do that. Okay. Move on then. Okay, BC? Mood instability and anxiety symptoms are common at treatment entry, and sometimes it's impossible to tell whether that's coming from the withdrawal, especially when they're withdrawing from the opioid withdrawal. Obviously, you are going to see the autonomic instability, and you may have some of the emerging... So we'll be talking about psychiatric comorbidities and pain management. I know a lot of our patients have pain as a comorbid medical condition. Some of them may have started using opioids as part of a chronic opioid therapy, and they developed opioid use disorder on top of that. Some of them have developed pain after developing opioid use disorder, and that may be bothering them, and that may continue to be the triggers for them. So hopefully we'll be addressing some of the questions about that. The objectives for this hour is to diagnose and discuss appropriate treatment of co-occurring substance use and other psychiatric disorders. Discuss strategies for treating acute perioperative and chronic pain for patients taking buprenorphine, describe appropriate treatment of opioid use disorder during pregnancy, and discuss appropriate treatment of opioid use disorder in adolescence. We'll just be talking about how SSRI and MDM is not making the substance use disorder outcome better or worse. But as you can see, if there are mental illness and substance use disorders in the United States, they have a lot of buprenorphine or overlapping long-acting naltrexone. And among those, there's no evidence that the SSRIs or other psychiatric medications would not be helpful for them, have both the substance use disorder and mental illness. Trauma and substance use disorders. So probably the PTSD is the biggest comorbidity that I see in my patients with substance use disorders. There used to be a – well, there are, I guess, still three schools of thoughts. Usually anxiety symptoms are common in treatment, and usually sometimes it seems possible to tell whether it's coming from either PTSD or trauma-related disorder first. And they'll be self-medicating their symptoms with the substances, and in turn they'll develop substance use disorder, some emerging PTSD. The second school of thought said that actually people with substance use disorders, they expose themselves in a more traumatic trauma-prone environment. If they're getting into bar fights, if they're getting into accidents, if they have to deal with dealers, if they are finding themselves in a situation where they have a role in their work as a sex worker to afford their substance use, then it makes sense that they'll sustain trauma and develop PTSD. The third school of thought will say that actually both can be true, but maybe there's a common genetic disposition to make them susceptible to develop substance use disorder and or PTSD at a similar rate. I mean, some of the research will show that they will have – as long as you are getting the HP axis, we talked about how SSRI and lifting HP axis is not making the substance use disorder outcome better or worse. But as long as they're stabilized, when you evaluate the research, such as longitudinal or longitudinal track zone, then there's no evidence that the SSRIs or other psychiatric medications will not be helpful to them. So that's the self-medication hypothesis. That the patients have developed trauma and substance use disorder. So probably the PTSD is the biggest comorbidity that I see in my patients with substance use disorder. And it goes back to the point that the writer made. When you're trying to engage patients to make a change together, usually the patients will have trauma and they'll have either PTSD or trauma-related disorder. And at one burst, they'll be self-medicating their symptoms with the substances, and in turn they'll develop substance use disorder on time. Second school of thought, people with substance use disorder, they expose themselves in a more traumatic trauma-prone environment. It can kind of help focus your treatment approach. So that is something that we're going to continue to talk about. If they are finding themselves in a situation where they have to work as a sex worker to afford to their substance use, then it makes sense that they'll sustain trauma and develop PTSD. The third school of thought will say that actually both can be true, but maybe there's a common genetic disposition to make them susceptible to develop substance use disorder and or PTSD at a similar rate. Some of the research will show that they will have the HP axis. Comorbid illness is more difficult to treat than either individual disorder. When you evaluate the evidence, when you evaluate the research, just because you treat the PTSD doesn't guarantee you that their substance use disorder will improve on its own without the substance use disorder treatment. By all means, I think that the patients have developed, they have sustained trauma. If you want to get their targeted PTSD treatment as soon as possible, the conventional wisdom used to say that because the point Dr. Renner made, when you talk about when you're trying to engage patients to make a change together, sometimes we exploit, what does it do for you? Then they'll relapse. At one point, substances, especially in cases with severe PTSD and severe substance use disorder, if you want to make sure that they have their substance use disorder, but just recognizing and validating and being able to reflect on the fact that the substance use disorder at one point was helpful to them, it can kind of help focus your treatment approach. That is something that we're going to continue to talk about, and we're going to target after we stabilize substance use disorder or even during the stabilization period of opioid use disorder. The prevalence of lifetime PTSD in patients with a substance use disorder ranges from 26% to 52% concurrently. I just cannot stress the fact enough that the least substance use disorder being on medication for opioid use disorder really breaks or mimics the recovery. If a patient got into recovery for opioid use disorder, but they're not on medication for opioid use disorder, and they're just telling you that they're ready to now take a— but not vice versa. Just because you treat the PTSD for their sexual trauma from 10 years ago, that their substance use disorder will improve. I'll share my concern with them. Now, by all means, getting stabilized on medication for their opioid use disorder, the more evidences are showing that these are some of the things that you should be worried about, but I'll be here to walk with you. I'll be here to walk with you. Because they're self-medicating their PTSD symptoms with a substance use disorder, if you attempt to gain prior information from other providers too early that's a given point. That was the conventional thought. Your states will actually dictate how often you should minimally check your state PDMP. And if their severity of opioid use disorder is worse than others, then maybe you're checking more often. I'm very thankful to the public health effort that has become very, very difficult to doctor shop. We hear stories of patients having to travel multiple seeking state lines to obtain opioid prescriptions or benzodiazepines. So avoid use of benzodiazepines. It's not going to preclude me from providing buprenorphine treatment. I just cannot stress the fact enough that at least for opioid use disorder, at least for medication for opioid use disorder, really breaks or makes the recovery. So if a patient got into recovery for opioid use disorder, but they're not on medication for opioid use disorder, and they're just telling you that they're ready to now take an increased risk for respiratory infection or overdose, then just slow down their breathing. But we know that this by itself is probably not going to kill a patient. I'd be nervous. Buprenorphine is the same token. It slows down their breathing. It does slow down breathing. You're not going to get me wrong. Buprenorphine does slow down the breathing, but there's a ceiling effect. These are some of the things that you should be worried about. It doesn't slow down breathing enough to be fatal to an adult. Now, when both are combined, they either work at different signal chains for respiratory depression, and sometimes that creates a synergistic effect of respiratory depression. The first line of treatment for anxiety and depression, as long as they're on medication for opioid use disorder or the other substance disorder, same thing, select the SSRI or the SMRI, and plus psychotherapy, especially if they're on board with that. Stimulants. If there is a concern for attention deficit ADHD, it has become very, very difficult to doctorate these days. If you are the psychiatric consultant and you've had the psychiatric assessment, then you'd be doing it yourself to obtain opioid prescriptions or benzodiazepines. If the diagnosis has been definitely established, I will say that there is more and more evidence that providing buprenorphine treatment, just because they're on benzodiazepine prescriptions or they're using benzodiazepines stimulants can mitigate, at least from the autopsy, from the post-mortem studies for substance disorder and or incarceration risk. And if they have definitely established diagnosis of ADHD and they've benefited from HSB, polysubstimulant medication, by all means, continue it. Associated with more erratic behavior, increased risk for respiratory depression, overdose, then just slow down their breathing, but we know that they're not asking for stimulus just because they're not gonna kill a patient. I do ask for collateral information. Buprenorphine, the same token. And it slows down their breathing. It does slow down, it doesn't help everyone who's struggling with an opioid disorder, but when it does, it's been the missing ticket. It doesn't slow down their recovery all along. It's treating their ADHD. Now, when both are combined, they either work at different signal chains for respiratory depression. It can sometimes create a synergistic effect of respiratory depression. The first-line treatment for anxiety and depression, as long as they're on medications for opioid disorder or other substance disorder, same thing, so it's the SSRI or the MSRI. Full disclosure, I'm not a pain doctor. I'm a psychiatrist. I'm a therapy psychiatrist. I'm not our own board with that. So I'll be talking about what we know from the research and my experience with my patients who've been, who had a flare-up of acute pain. If you are the psychiatric consultant, if you had a psychiatric assessment, then you'd be doing it to yourself. If continued stimulants, if the diagnosis has been definitely established, I will continue the same buprenorphine dose, but in a split regimen. So there's more and more evidence that the clear answer from persistent, stable, but for some reason, buprenorphine is given as a stimulant and a splitting dose. It's more helpful as an analgesic. Future risk for substance use disorder and or incarceration risk. And if they have a definite craving purpose, it's dispensed once a day. Or if they're a fast metabolizer, then sometimes they'll continue it. But when this methadone is prescribed, methadone is legal to be prescribed to for treatment of pain. They're not asking for stimulants just because they're in a hurry or they don't want to do it. So for buprenorphine as well, if they're on 16 milligrams of buprenorphine, in my experience, it doesn't help everyone who's struggling with the opioid disorder. But when it does, it's been the missing, like while keeping the same part of their recovery all along for the entire day, I'll suggest them to take four milligrams four times a day first. Attempt to facilitate treatment in an integrated care setting. To most often, that is equally helpful. Manage reduction in use and for many abstinence, and for many patients. You can then supplement that with the NSAIDs and NSAID-aminophen. If they're still continuing to complain of increased pain, then you can temporarily increase the buprenorphine dose. Full disclosure, I'm not a pain doctor. I'm a psychiatrist. I'm an addiction psychiatrist. I'm not an anesthesiologist. Opioids, so I'll be talking about what we know from the research, except my experience with my patients who've been, you know, who had flare-ups of acute pain and were going through operations. But the other is okay. You can use buprenorphine that's only approved for acute pain to use as an opioid label to treat pain. So you use medications off-label all the time, but in a split regimen. So I haven't got a clear answer from an opioid disorder. You can still use that off-label to treat your pain. You know, and I do that all the time. If a patient is having acute flare-up of their acute pain or their chronic pain or they have developed some surgical condition and they're waiting for their surgery or if they're a fast metabolizer, then sometimes they'll split the dose and kind of target the pain. But when this methadone is prescribed, that's all legal to be prescribed. That's usually done in a control setting when I'm talking about control setting, usually in an inpatient setting. When the medication is prescribed to them, if they're on 60 milligrams of buprenorphine and let's say they had a pain, they had just had a dental procedure where they had developed, you know, they pulled it back. Stop buprenorphine and initiate full agonist therapy while keeping the same buprenorphine dose, the same for the entire day. So I'll suggest them to take four milligrams, four times a day first to see if that's helpful. But sometimes they're gonna, maybe they're anticipating a very invasive surgery. We're talking about like, you know, open heart, you know, you can then supplement that with the, you know, endocarditis. If they're still continuing to complain of increased pain, they're gonna be temporarily increase the buprenorphine dose for several days or weeks. It is not allowed to use opioids. Obviously you're not gonna do this as an outpatient setting. Except buprenorphine parts that's approved for opioids. Now it used to be that there was an old recommendation that if any patient on buprenorphine was gonna go into a surgery, stop the buprenorphine three days before the surgery so that they can use it as an overlabel to treat pain. So if you use a medication that's off-label, you do not recommend that. So using buprenorphine part of this is the advice that it doesn't lead to bad outcomes. Patients complain of no control symptoms, increased pain, you know, and I do that all the time. And you lose them from the treatment altogether and you're afraid of their acute or chronic pain or their relapse. So we don't recommend that. They have developed some surgical condition and they're waiting for their surgery. Patients fear mistreatment. That is very real. So we were talking about the perioperative management of buprenorphine. You know, if they're talking about elective surgery, when I'm talking about control setting, usually fear mistreatment from their surgery medication or anesthesiology team, nurses dispensing medication to them directly, and they're my patients on buprenorphine. It doesn't matter if they've been on buprenorphine for five years without any relapse, they'll, you know, a lot of providers will feel like, oh, you know, they're gonna lie to me. Are they gonna try to ask for more opioids? So there's a fear in both ways. Maybe they're anticipating a very invasive surgery. We talked about like, you know, recommendations and the survey of the existing protocols and algorithm. And we'll talk more about that tomorrow if they're gonna be on a QPAC or a QPIM for several days or weeks. Then maybe it's beneficial to just stop your patients on six milligrams of buprenorphine should be done. Obviously you're not gonna do this before their surgery, as an outpatient setting, you know? Now, it works best that you plan this preoperatively. There was an old recommendation that if any patient on buprenorphine was gonna go into a surgery, stop the buprenorphine three days before the surgery so that they can take their own high-dose buprenorphine. A lot of academic hospitals have their pain consult team and they'll be consulting them beforehand and they'll be consulting you. And hopefully you'll come up with a plan together with increased cravings, increased pain, and hopefully you'll be on a good plan to go forward. Which is part of the reason for their relapse. So we don't recommend that. So if the patient is already on partial agonist buprenorphine there should be strong consideration for continuing buprenorphine on consultation with surgery. Like I said, stopping buprenorphine, not recommended, especially if they're talking about a negative surgery. Especially if the buprenorphine is less than 60 milligrams it still gives a reasonable vacancy in the mu-OP receptors to be occupied for the purpose of the operation. Alternatively, it doesn't matter if they've been on buprenorphine for five years, if it's going to be relapsed, the patient's going to require a high dose of buprenorphine. They're going to be full agonist. The opioids are going to try to ask for more opioids. So there's a fear in both ways. And there's a lack of consensus. There are some, we do know that the recommendations is minimal in the survey. It's not enough time for the patient to go into full blown opioid withdrawal because they stopped buprenorphine. And the buprenorphine is a long-acting carcinogen. There's no CDC guideline to say, oh, patients on 60 milligrams buprenorphine should be done and done. And by the time they get the surgery, they'll be intubated and they'll be getting full agonist opioids to treat their pain and their discomfort as well. It works best if the surgery team has recognized that this is going to be a complex pain or this is going to be a little bit more complicated because of their own high dose of buprenorphine. A lot of academic hospitals have their pain consult team. And maybe you'll be in the place to provide that recommendation with the surgery team, look, just because the patient is reporting to me that 10 milligrams total of oxycodone you'll be able to agree on a good plan to go forward does not mean the patient is drug seeking. So if the patient is already on partial agonist buprenorphine, there should be strong consideration for continuing buprenorphine on the consultation with a third dosing to treat their acute pain. Like I said, stopping buprenorphine, not recommended. We do know that if, especially if the buprenorphine is less than 60 milligrams, we still get an optimized dosing with a full agonist as indicated for breakthrough pain as indicated to be occupied for the energetic purpose during the operation. And because, alternatively, if you think that this is going to be authorized, the patient is going to require a high dose of any other full agonist treatment on top of that. And the anesthesiology team feels nervous about having the buprenorphine on board, and then the most tolerated will suffer. Or you could consider, do you know that maybe he was on 60 milligrams of buprenorphine before the surgery? Is not enough time for the patient to go into full-blown opioid withdrawal because they stopped buprenorphine. Buprenorphine, if there is a long-acting partial agonist, they may, like I said, more frequent partial agonist dosing, split, but they will not go into acute opioid withdrawal. And by the time they get the surgery, they'll be intubated, and they'll be getting full agonist opioids to treat their pain and their comfort as well. And you counsel the patient, look, you don't want to invalidate their reports of suffering or pain. So at the same time, you can say, look, you're higher than normal, you need a replacement after your hip replacement. And maybe you'll be in the place to provide that recommendation of the surgery team. Look, just because the patient is reporting to you that the 10 milligrams total, I'm never saying never, 24 hours is not helpful, does not mean the patient is drug-seeking. It may mean that the patient has developed high tolerance from being on buprenorphine treatment. Another option is to, especially if they, like I said, I gave an example of an open heart pain, aortic valve replacement, and they're gonna be in the acute rehab for a long time, and they're gonna be in CBRT for a long time, then maybe you can just continue partial agonist dosing with a full agonist, as indicated for breakthrough pain, as indicated for this pain. It's a little bit tricky, because they have developed the tolerance from the OP, you know, to OP, in general, because buprenorphine prescription and any other full agonist treatment on top of it, transition that back to buprenorphine. They'll have to go through partial agonist dose as tolerated postoperatively. So that's not the most comfortable feeling. You know, he was on 16, you know, maybe he'll be done as in the rehab as an inpatient setting so as to not to expose him to unnecessary risk as an outpatient basis. So the postoperative pain after they were discharged from the hospital, like I said, more frequent partial agonist dosing, and again, adding a short-acting full agonist on top of buprenorphine may be problematic with the surgeon, or, you know, with the insurance company. Obviously, I'm not gonna be the one to give them full agonist opiates to treat their pain. Look, you're, you know, not to, you know, you don't wanna invalidate their reports of suffering or pain. At the same time, you can say, look, sure, there's gonna be a risk if you have a hip replacement after your, you know, transitioning from buprenorphine to full agonist back to buprenorphine. I expect you to be on the buprenorphine dosing in two to three weeks. I'll work with you, and it's, you know, never say never. So far, so good. But that's my expectation, that's my, you know, course, and if you can speak in the mic, then maybe, you know, every, you know. That's a very good question. I, you know, asked, actually, like I said, multiple pharmacists, and I actually, you know, asked the buprenorphine replacement companies, and they're gonna be in the acute rehab for a long time, and they're having severe pain for a long time, and maybe a discontinued partial agonist would have to provide additional full agonist to treat both pain, and also to try to control their cravings. I'll get you a mic, because they have developed typically from the sublingual administration, buprenorphine plasma levels are at about one hour, one to two hours, and we know that people get more analgesia with a higher plasma level. So then you're gonna get a very gradual decrease over 24 hours, and probably you're gonna be around two nanograms per ml on a higher dose of buprenorphine, like 24 milligrams at 24 hours. But what we want to do for the analgesia is to get them some increased peaks, so we're really having better pain relief at those peaks, and that's why, that's the rationale for dividing the dose for people who have either acute or chronic pain. It's gonna be coming from their, you know, surgery team. Thank you, Dr. Saxon, and it makes sense, because, so with the, you know, with the relapse medication, as you laid down all these different options between the, you know, the, once it's gonna be a risk, if you have any dosing, but the peak level will be going here, and maybe they can only get the analgesic effect from the peak level of certain level, and we'll, and maybe we can target that to make sure to provide extra support for you. Yes, no, thank you, thank you for your comment. So, buprenorphine injection, the brand name Sublocade, you know, has been around for about the last three years, and, you know, we will actually be talking about the perioperative management on patients on buprenorphine, but in Canada, they're using buprenorphine injection. Canada, is that right? Okay, did I get your country right? Thank you. And they're using, also, additional buprenorphine, supplemental buprenorphine on top of that. Now, from the anesthesiology perspective, they can utilize the regional block, they can, you know, utilize, you know, epidural anesthesia, and to continue to help them with them, but that's the, we'll talk more about that tomorrow, okay. I'm gonna move on to the next slide. Patients currently on naltrexone, what their acute pain management will be. So, the acute, you know, naltrexone, we're gonna be talking about patients on naltrexone, long injectable, because oral naltrexone, I don't know if, actually, we ever discussed the oral naltrexone, how it's not recommended for opioid use disorder. It does have FDA approval for opioid use disorder, oral naltrexone, however, from subsequent studies, we've seen that it does not make a difference, either statistically significant or clinically significant outcomes for opioid use disorder. So, if you're gonna provide naltrexone for their opioid use disorder, it's gonna be either long acting injectable naltrexone, or, you know, consider something else. Now, oral naltrexone, their levels of medication will be, you know, kind of becoming to null by the end of the day. So, this is the patients on long acting injectable naltrexone that has had, that's having pain. Just to repeat the same principle, you wanna maximize the NSAIDs and the acetaminophen and everything, you need to go through that. Yeah, scheduled surgery, elective surgery is, if it's up to two hours, right? And we know that people get more analgesia with a higher plasma level, and so then you're gonna get a very gradual decrease over 24 hours, and probably you're gonna be around two nanograms per mL on a higher dose of buprenorphine by 24 hours. And you'll be counseling the patients, look, you can understand that the oral naltrexone is not as good, actually, it's kind of useless, to kind of treat their opioid use disorder. In your case, but you're not currently struggling with their opioid use disorder, and you're on a stable dose, and because you're going through elective surgery, we wanna optimize your pain, because increased pain, or inactively controlled pain, so it can be a powerful trigger for opioid relapse. Therefore, once you transition to oral naltrexone, the peak levels will be different, and maybe they can only get the analgesic effect from the peak level of surgery, with the additional monitoring and additional support as needed for this case. And major pain or emergency, I talked about regional anesthesia, you know, in a conscious station. Even with Vivitrol, Vivitrol is the brand name for the long injectable naltrexone, it can still be overcome, especially after the third week or the fourth week, with a high dose of fentanyl. It may be that their surgery team may be still nervous about giving them this much of the opioids to overcome the blockade. So you gotta counsel the patient, look, it's gonna be a learning process for them, too. Now, for this reason, I've had patients declining long injectable naltrexone, because of fear of acute, unexpected injury. One of my patients, I talk, I ride a motorcycle, and I fear that if I get into an accident, and I'm not gonna get my pain adequately controlled, and that is a very valid concern. Thank you for your comments. So, buprenorphine injection, the brand name Subloc-P, has been around for about the last three years. We will actually be talking about the perioperative on patients on buprenorphine, but in Canada, they are using buprenorphine injection in Canada, and he didn't wanna take the long injectable naltrexone, then reluctantly, I agreed to it, okay, then I'll go on top of that. Now, from the anesthesiology perspective, they can utilize the regional block, they can utilize epidural anesthesia, and to continue to help them with that. As I mentioned, the methadone is kind of similar as buprenorphine, when it's prescribed for analgesia, it's broken up into TID, curative dosing. Patients currently on naltrexone may require higher dosing of methadone and higher dose of buprenorphine, if they're experiencing acute pain while on methamphetamine. We're gonna be talking about patients on naltrexone, if a patient, for example, if a patient on naltrexone, I don't know if actually we ever discussed the oral naltrexone, how it's not recommended for opiates, that patient does have FDA approval for opiates disorder, 200 milligrams of methadone is not recommended for opiates. From subsequent studies, we've seen that it does not make a difference. Obviously, you're not gonna be managing them as an outpatient and hopefully your hospital, for opiates disorder. If you're gonna provide naltrexone for their opiates disorder, it's gonna be in either long-acting, injectable naltrexone or consider something else. Now, oral naltrexone, their levels of medication will be individuals treated with the opiates disorder by the end of the day. So this is the patients on long-acting, injectable naltrexone, this is for the chronic pain. This is, just to repeat the same principle, if you wanna maximize the NSAIDs and everything, memorize the phrase by now, because your non-pharmacological therapy is far out. This is a typical, like three weeks out, four weeks out, that's easier. You wanna transition to oral naltrexone, some limited evidences for chronic pain, and you wanna discontinue oral naltrexone. It's not mentioned here, but consider referring them to cognitive behavioral therapy for chronic pain. And you'll be counseling the patients, but you can understand that the oral naltrexone is not as good of a talk therapy option for their pain, because they're insulted. They think, in your case, but you're not currently struggling with the opioid use disorder, you know, you're on a stable dose, that's not because you're going to do elective surgery, you're gonna optimize your pain, because additional, because increased pain, or any other pain can be also a trigger, it can be a powerful trigger for opioid relapse. Therefore, less, have you, you know, oral naltrexone, our, you know, most, and stops three days before the surgery with the additional monitoring and additional support as needed for this case. And you had to go to work tomorrow, what would you do? You'd take the day off. And if major pain or emergency, hopefully you'll get better in a day or two and then you'll go back to work and you'll be fine. If you felt pain for something and you had a plan for the night, you'll call that off and you'll just stay home. Now if you had deep pain for the last 10 years every day, and if you use the same coping strategies to pull out of work and to cancel social gatherings, what's going to happen is that you're going to be more isolated. You're going to be unemployed. You're going to be dealing with a lot of difficulties and you're going to be more inactive. Now for this reason, I've had patients declining long-acting injectable naltrexone and because of fear of acute, unexpected injury, I've done maladaptive behavioral strategies to make sure that if I get into an accident, I'm not going to get my pain out of control. That is a very valid concern. However low their incidence, the accident risk may be, it is his concern and I felt that he felt that. Then I talked to him about alternative options. Maybe I know their particular patient had very strong belief against any agonist treatment and he didn't want to take the long-acting naltrexone. Then reluctantly I agreed to, okay then we're going to just go with the effective strategies and just therapy options to help your recovery. So that is the end. As I mentioned, the methadone is kind of similar as the buprenorphine. We'll take a 15-minute break. Thank you for your attention. We'll resume in 15 minutes. Thank you. Okay, here we go. We really are in the home stretch here. Eight hours is a long, long time. If a patient, for example, you think you're tired, I'm probably even more tired. So I'll do the best I can. But we've got a talk, another case, and then one more talk, I believe, and then we'll have time for questions. So the next part is on pregnancy and medical comorbidities. So we're going to start with pregnancy. The very obvious point is we're all psychiatrists, so none of you are going to be providing the prenatal care, I presume, so if we're treating pregnant patients, you may be needed to manage their opioid use disorder and their co-occurring psychiatric disorders and their pre- and postpartum depression, et cetera, but we all want to be working with an obstetrical clinician who's going to handle the actual OB work. So actually, sadly and not surprisingly, substance use is not all that uncommon in pregnancy. It's not mentioned here, but consider referring them to cognitive behavioral therapy for chronic pain. Opioids is not all that uncommon. It is a very effective intervention. Many patients will bulk it, using it, about one out of five of them report misusing it, so we do see more than we would like opioid use disorder occurring either pre-pregnancy or during pregnancy, and actually the American Academy of the American College of Obstetrics and Gynecology recommends screening all pregnant patients for substance use disorder, and actually there's a recommendation for all adult patients. They say it should be screened for, certainly for alcohol and tobacco, but they made this recommendation using it for drugs, although it's hard to know. There isn't a lot of evidence for the screening for drugs, but among pregnant patients, we're talking about two lives, and so it is probably worth doing that. And now if you had that pain, for the last 10 years, every day, and if you used the same coping strategies to call out of work and cancel social gatherings, what's going to happen is that you've got to be more isolated. You've got to be unemployed. You've got to be feeling the financial difficulties. In turn, you're going to be more inactive. You're going to make the pain worse. You're going to make your existence worse. The first-line treatment for buprenorphine came along, and it was very clear from studies that pregnant individuals with opioid use disorder who were treated with methadone had much better outcomes than those who were not treated with methadone. So that became sort of the standard of care. Now we've done a lot of research, some of which I'll present to you, comparing methadone and buprenorphine, and they both work better than no medication alone, and so they both are the standard of care. With methadone, for sure, we know that the metabolism of methadone is increased during pregnancy and the volume of distribution is increased, and particularly in the second and third trimester, it's very common for pregnant persons to need higher doses of methadone. We'll take a 15-minute break. Thank you for your attention, and we'll resume in 15 minutes. Thank you, everyone. That actually can be difficult to do in the setting of an opioid treatment program because some of the programs are uncomfortable, especially if the patient's on daily dosing, getting half the dose under observation and then giving them a half to take home. But sometimes it's really hard to stabilize these patients without that. We know a little less about whether the dose of buprenorphine needs to go up, but in my opinion it's really important to be attuned to that. We talked about how we tell what the right dose is, so if in the latter stages of pregnancy we have a patient who was stable on a given dose and now the patient's saying, or I feel a little like I might have withdrawal, it's probably worth increasing the dose of buprenorphine and or doing split dosing if that wasn't happening before. There was this belief that we should use the monoproduct for pregnancy, that is just buprenorphine alone without the naloxone. The idea for that, which Dr. Park already described, is that some naloxone does get absorbed, it does cross the placenta. We're exposing the fetus to a substance that we don't know the effects of on the fetus, and why do that if it's not necessary? We can just use the plain buprenorphine. As things have evolved, experts in treatment of pregnant persons with opioid use disorder have gone ahead and used the combination product, and observationally we haven't seen any problems with that. So in 2023 it's fine to use either one. We talked earlier about using the monoproduct and pregnancy aside, there are some patients who are going to say they can't tolerate the naloxone, they want the monoproduct, and it's okay to do that. Probably even more okay in pregnancy because you have the reason that we don't know if naloxone is going to be harmful to the fetus, we don't have any real evidence that it would be, but I'm just being ultra-cautious. But it's also fine to start the combination product, and we haven't seen any problems with that. So if you have a patient who you were treating who becomes pregnant and that patient was on the combination product, I think it makes sense just to continue that rather than change at this stage of the game. So it's really relatively safe in pregnancy. Now, if you have a pregnant person with opioid use disorder who's not on any medication, it's in some ways trickier to start that just because we don't want to expose the fetus to a lot of withdrawal. And one of the problems with not treating pregnant persons with medication is if they're using illicit opioids, they're going to go through a cycle of being intoxicated and being in withdrawal. So we're exposing the fetus to this real extreme seesaw effect. So if we're going to be starting medication, buprenorphine de novo, clearly the patient has to be in some withdrawal, but we don't necessarily want to get that patient into severe withdrawal. So it's going to be a little bit of a balancing act. And what the slide's saying is the farther out they are in pregnancy, the more challenging it might be, and the more withdrawal or precipitated withdrawal might adversely affect the fetus. So probably don't do a home initiation and maybe even consider admission for that, which is probably with all the minders we have telling us how to use our resources, that might be challenging, but at least advocate for it. So it says here the dosing is the same as in non-pregnant women. Typically, yes, but, again, have a low threshold for increasing the dose if it seems clinically important. We're about to define the acronym NOWS, which is Neonatal Opioid Withdrawal Syndrome. And so the point here is that's a phenomenon that I'll talk about in a second, and it makes sense. If the fetus is being exposed to either illicit opioids, methadone or buprenorphine, the fetus is going to develop physiologic dependence potentially, and when the baby is born there could be opioid withdrawal. And so the NOWS is Neonatal Opioid Withdrawal Syndrome. But the important point here, the severity of that syndrome has no association with the dose of buprenorphine that's used. So we don't want to be, oh, I'm worried about the baby having withdrawal, so I'm going to keep the buprenorphine dose. No, we want to treat the pregnant person fully and optimally for opioid use disorder, and we're not going to worry about the Neonatal Opioid Withdrawal Syndrome until we have to confront that. So it mentions, again, what I said about possibly increasing the dose. Postpartum, continue the current dose. If you did raise it during the third trimester, it might be possible you can drop it down again. The nice thing, again, about buprenorphine is we have this safety threshold, so if postpartum the patient happens to be on a dose that's a little too high, maybe there will be side effects, but it's not going to put that person into an overdose, as could happen potentially with methadone. And if you did convert to mono, you could go back to the combo product or whatever the patient prefers. So in regard to the nows, we're seeing more and more of that simply because we're seeing more. We've got the opioid epidemic, and pregnant people are as vulnerable to all the opioids around as anyone else, so we are seeing more pregnant persons who have opioid use disorder. And most of the neonates are going to have some degree of nows, and about 50 percent will need treatment, so some may have a very mild case, some have a more severe case. And obviously we can't talk to the neonates about what their symptoms are, so we only know what the signs are, which are the irritability, fever, diarrhea, hyperreflexia, even seizures. It's going to begin a day or two after the birth as whatever medication or substance the mother was using comes out of the neonate system, and it's going to peak maybe three or four days afterwards and can continue on a little bit. And the worst cases we're going to see are the pregnant persons who are using illicit opioids, and they can actually have a lot of pregnancy complications, which are much reduced with methadone or buprenorphine. So this is a landmark study called the Mother Study that was published in the New England Journal of Medicine, and this is really the study that established buprenorphine as a first-line treatment for pregnant persons with opioid use disorder. So it was a double-blind, double-dummy, randomized trial done essentially in opioid treatment programs where the patients were coming in almost daily to get observed dosing, and so they got a liquid drink, and this was before the film strips were available. They got some pills to put under their tongue, and depending on which condition they were assigned, one was a placebo and one was active medication. And what they found is a pretty big impact of using the buprenorphine and the neonatal opioid withdrawal syndrome in that if the mother had been treated with buprenorphine, the infant had a less severe form of the withdrawal. And in this study, they treated the neonates who needed pharmacologic treatment with morphine. And so you're looking at the total amount of morphine over the course of the withdrawal episode, and you can see how much less morphine the infants whose mothers had received buprenorphine needed compared to the infants whose mothers had received methadone. The middle panel is their hospital stay in days, just slightly over half for those treated with buprenorphine, and the right panel is the duration of—here it's called neonatal abstinence syndrome. That used to be the old acronym, so the duration of treatment was less for the infants whose mothers had been treated with buprenorphine. I just will say parenthetically that I talked to Dr. Jones, the first author on this study, who's a psychologist, but she's probably one of the world's experts in treating pregnant people with opioid use disorder. And she actually—although we switched to NAWS from NAS, she actually prefers NAS, and I said, well, why? And she said because very rarely are the mothers using only one substance, opioids, and so we're actually seeing infants withdrawing from more than one substance, and so she prefers that. But whether you call it NAS or NAWS, that's what we're confronting. So we'll go back to calling it NAWS. What is the treatment? So we really revised what we do in the last five or ten years. What used to happen is the baby was whipped away from the mother, put in the NICU, given—we don't even know the best medication. Some places used morphine, some used a tincture of opium, some used methadone, but treated pharmacologically. And we found out that that's probably the worst approach because you're interfering with mother-infant bonding and it's just really disruptive to the dyad. So now we're trying to go to the eat, sleep, and console protocol, and we're trying in most cases, even if the infant is exhibiting NAWS, to do rooming in if possible because we're finding that the infants do much better and the mothers do much better if they're together rather than the infant being in the ICU. So here's the how do you determine what to do. If the infant can eat or breastfeed, then that's good. If not, then we might need increased non-pharmacologic interventions, which is feeding on demand, swaddling and holding, a low-stimulation environment, and of course hospitals are the least low-stimulation environment we could imagine except for the exhibit center across the way. So that's tough. And again, the rooming in or having the parents involved. If the infant can eat, can the infant sleep more than one hour? If the answer is no, we go to those other non-pharmacologic interventions. If the answer is yes, we ask can the infant be consoled within 10 minutes by hugging and cooing at the baby just like we would do with any, those of us who are parents have had or grandparents have had the experience of an infant who can't be consoled, which is very unpleasant and upsetting, but it happens. But if we can get them feeling better in 10 minutes, then we're okay. And then we can say if all those three things are true, the baby can just stay with the mother and the mother will work on this, no other interventions or pharmacologic treatments are needed. If the increased non-pharmacologic treatments, the feeding on demand, swaddling and holding, low-stimulation environment, et cetera, are not improving the situation, then we're going to go to the pharmacologic treatment, and that's not something any of you would be probably ordering because you're, I don't, unless someone's also a pediatrician here, but it's good to know that right now we're suggesting morphine as the pharmacologic treatment. So that's how we're going to manage that, and I guess your role would be to coach your patients and explain to them what's going to happen, and if for some reason the hospital where they're giving birth is doing things the old-fashioned way, you might need to educate the people there about how it should be done in 2023. Breastfeeding is encouraged with the patients on any one of the three medications for opioid use disorder. We don't see a lot of the medication getting into breast milk, and so that's fine. In fact, there's not even enough in breast milk to treat the neonatal opioid withdrawal syndrome. So whatever minimal exposure the infants get to these medications is far made up for by the fact that breastfeeding is so much preferred to formula feeding in terms of the health benefits, and also we've had formula shortages recently, and that could happen again. So breastfeeding makes you not have to worry about that. Are there any questions about pregnancy? During the postpartum phase, so when they're breastfeeding, is there any preference for Subutex or Suboxone? Can you repeat the question? The question is, for the breast, during the breastfeeding stage, is there any guidance or preference for Buprenorphine or Suboxone? No, no. It's fine, fine to use either the mino or combo product. We're going to start up again in about 30 seconds, maybe 45 seconds. And typically we'd say postpartum, the combo product, unless there's some objection to that. But yeah, that shouldn't be a problem with breastfeeding. Is there any current data regarding the pregnant patient on sublocate? Oh, sublocate for pregnancy, good question. Sublocate for now is contraindicated in pregnancy because there's an excipient in the sublocate that is teratogenic. So, do not use sublocate in pregnancy. Okay, here we go. But we really are in the home stretch here. We hope in the future we will have a long, long time injection that is safe for pregnancy. I'm probably even more tired. As I understand it, that Braeburn product that hasn't come on the market yet, the one week injection is probably okay in pregnancy, and actually that's being studied right now. Then we'll have time for questions and discussion. So the next part is on pregnancy and medical comorbidities. So we're going to start with... Okay, so the question is what if the patient's already on sublocate and we find out the patient's pregnant, what do you do? Very obvious point is we're all psychiatrists, so none of you are going to be providing prenatal care, I presume. So, the patient's on a medication that has a teratogenic compound in it. What would you do? What I would do is I'd probably switch, as much as I have a strong opinion thinking that sublocate is a top treatment right now for opioid use disorder in the fentanyl era, I think that I would switch back to the sublingual buprenorphine, because I don't want to personally be responsible for a malformed fetus that's just in a very unhappy situation. Opioids is not all that uncommon, and among the 7% who report using it, about one out of five of them report misusing it. So we do see more than we would like opioid use disorder occurring during pregnancy or during pregnancy. We're not seeing any rates of fetal malformations or anything like that. Higher than the normal population. Higher than the normal population. What we see in the normal population, so the far bigger risk is not treating opioid use disorder with medication, then you're going to have a lot of complications. So yes, you're not going to be sued if you treat a pregnant person with buprenorphine, and there is an adverse outcome. I mean, you could be sued, but you're not going to lose that person. We're talking about two lives, and so it is probably worth doing that. And I'm sorry, because the speakers are faced the wrong way, it's really hard to understand the screening instruments that are mentioned there. It probably wouldn't be you doing the screening unless a pregnant patient is coming to you for other psychiatric disorders, in which case you should make sure that there's no requirements that they be on contraception. Oftentimes it's the obstetrician. I do not know the answer. So people don't mind hearing from a drug company representative. She really has the information. So a methadone was the first line treatment before buprenorphine came along. And it was very clear from studies that it's very, very rare to have a pregnant individual with opioid use disorder who were treated with methadone had much better outcomes than those who were not treated with methadone. So that became sort of the standard of care. Now there's been a lot of research, some of which I'll present to you, comparing methadone and buprenorphine, and they both work better than no medication alone, and so they both are the standard of care. Methadone has shown negative fetal outcomes in animal studies, but there's no published data in human studies showing that. The levels they use in animal studies are much higher than that are used in sublucate as well. But we did not study this in pregnant patients, so it is a risk versus benefit. It should only be used when the benefits outweigh the risk. Very patient-specific. There is not a requirement to be on contraception that you ask. You asked as well. I should have known all that. I didn't, but I'm glad we have another knowledgeable person here, and it's great to be supposedly teaching the course and learn something while you're teaching it, especially if the patient's on daily dosing, giving half the dose under observation and then giving them half to take home. But sometimes it's really hard to stabilize the patient without that. We know a little less about whether the dose of buprenorphine needs to go up. So the question is, can you go back on the sublucate after the first trimester, which we know is that the fetus is basically forming the highest risk time for teratogenic effects. So again, I don't have the answer to that. You all can decide. My inclination would be to not use a medication that has an excipient that, at least among animals, has been teratogenic. I believe that we should use the monoproducts for pregnancy, but I don't want to take without the naloxone. And the idea for that, which Dr. Park already described, is that some naloxone does get absorbed, it does cross the placenta. I'm saying that as a fetus to someone who's about to have a second grandchild, and we don't know the effects of it on the fetus, and I have no reason why I'd do that if it's not necessary. I'm still nervous that everything's going to be perfect with the baby. Studies have evolved. Experts in treatment of pregnant persons with opioid use disorder have gone ahead and used the combination product, and observationally, we haven't seen any problems with that. So in 2023, it's fine to use either one. We talked earlier about using the monoproduct, and pregnancy aside, there are some patients who are going to say they can't tolerate the naloxone, they want the monoproduct, and it's okay to do that. Probably even more okay in pregnancy because you have the reason that you don't know if naloxone's going to be harmful to the fetus. We don't have any real evidence that it would be, but just being ultra-cautious, I really can't answer that. I guess, well, of course, I'll venture a guess, but I would say since we don't have any definitive information, so if you have a patient who you were treating, thanks to our knowledge of the person here that was on the combination product, I think it makes sense just to continue that rather than change at this stage of the game. Premature, until we have more information. And I will say it's really relatively safe for pregnancy. We're seeing increasing use of sublocade, but we haven't heard any reports. If you have a pregnant person with opioid use disorder who's not on any medication, it's in some ways trickier to start that just because you don't want to expose the fetus to a lot of withdrawal. And one of the problems with not treating pregnant persons with medication is if they're using illicit opioids, they're going to go through a cycle of being intoxicated, being in withdrawal, so we're exposing the fetus to this real, say, extreme seesaw effect. So every month, if we're going to be starting medication, whatever's... I mean, buprenorphine, we often say every month we're going to get a pure intox screen. In this case, the year of pregnancy test would be a lot more valuable. So whatever year withdrawal. So it's going to be a little bit of a balancing act. If I may add, often my patients with the worst, most severe form of opioid use disorder, I counsel them about the sublockhead injection, the buprenorphine long injectable. And as it was mentioned, it's about benefit-to-risk calculation. If this patient had already been tried on buprenorphine, naloxone, combo, mono, high-dosing, low-dosing, and she couldn't just stay sober, as opposed to... Actually, this has been her only time of recovery, being on the buprenorphine injection. Then I think that's different. There, I still have an option. So I could be on buprenorphine and still be in recovery, or be on a sublockhead buprenorphine long injectable and still be in recovery of a child their age, then I'll keep going with the buprenorphine sublingual. But I particularly have a patient, his entire life, he has struggled. And the only six months of recovery he had was on the buprenorphine long injection medication. Now, it's a he, but if it's a she, then I would not advise her to come off of a buprenorphine injection, but I will make sure and document this as well to make sure that I consult the patient about that. And I will involve their... The severity of that syndrome has no association with the dose of buprenorphine. So we don't want to be, oh, I'm worried about the baby having withdrawal, so I'm going to keep the buprenorphine dose low. Oh, I'm sorry. I'm glad that this is dealing so much discussion. And we're not going to worry about the area I'm least knowledgeable in, neonatal opioid withdrawal syndrome, until we have to confront that. So to conclude, patients who are female patients who are stable and who are on Suboxone for, say, five years, and have not had any relapses, they can go ahead and get pregnant. Oh, absolutely. Because, you know, oftentimes that's what happens with female patients. You know, they consider themselves stable, they have a job, they have a stable boyfriend, and then whatever. That whole point of getting patients on medications for opioid use disorder is to let them have high functional status and live their lives. They should live a full life with every activity available as anyone who doesn't have opioid use disorder. And if you did convert to mono, you could go back to the combo product or whatever the patient prefers. She just wanted me to mention, she'd asked about the peak level of that ingredient that is NMP, which shows the negative view of it in animal studies. And that peak is in the first 24 hours, and then it's pretty rapidly eliminated over the course of a couple days from the study. So I have to say, you two are having a discussion that none of us can hear, so if you're not going to speak into the mic, let's move on. So we're going to talk about youth opioid use, so we have a little graph here, some may have a very mild case, some have a more severe case. And obviously we can't talk to the neonates about what their symptoms are, so we only know what the signs are, which are the irritability, fever, diarrhea, hyperreflexia, even seizures. It's going to begin a day or two after the birth that was being pressed into these pills that looked like oxycodone that a lot of the youth are willing to experiment with what they think is a prescription opioid, and so it's going to peak maybe four days afterwards and can continue on a little bit. So we have to take account of that. So the American Academy of Pediatrics recommends for adolescent patients who have opioid use disorder that they do get medications. We're always worried about giving medications because the medications are still developing. But on the other hand, in my opinion, and in the opinion of the American Academy of Pediatrics, if we had a medicine version of opioid use disorder and we can intervene early and get young people stabilized, we might avoid a whole lifetime of persons with opioid use disorder. So it was a double-blind, double-thumbing, randomized trial done essentially in opioid treatment programs where patients were coming in almost daily to get a dose and so they got a liquid drink and this was before the film, equal or above 16. So starting at age 16 and depending on which condition they were assigned, probably in most cases, that's going to be your first choice for adolescents. You can see down below that naltrexone is approved for patients older than 18 and certainly can use it off-label in the neonatal opioid withdrawal syndrome in that sometimes if people want to go with naltrexone if you have an adolescent who's only had opioid use disorder for a brief time, maybe naltrexone will not expose them to further opioids. In this study, they treated the neonates who needed pharmacologic treatment with morphine at least in adults. You're looking at patients on morphine over the course of the withdrawal episode and you can see how much less morphine observational studies we have in youth suggest the outcomes are about equivalent morphine compared to naltrexone. But buprenorphine is probably going to be a very good first choice. Methadone is going to be much more challenging because as you can see here, for people under 18, not only do you have to get parental consent but they supposedly have to have what used to be the old acronym so the duration of treatment was less for those infants whose mother had been treated with buprenorphine. Just to say parenthetically, these patients on methadone, we have to be putting them through two withdrawal episodes. The first author on the study who's a psychologist but she's probably one of the world's experts usually in treating pregnant people with opioid use disorder. So buprenorphine is probably going to be our go-to generally. She actually prefers NAS. Any psychiatric disorder that we're treating adolescents for, we'd like to involve the family mothers using only one substance, opioids. We're actually seeing it's withdrawn from more than one substance and so she prefers that. Whether you call it NAS or NAS using the full array of behavioral interventions that Dr. Renner talked about. Go back to calling it NAS. That's all on youth and in a few minutes we can revise what we do in the last 5 or 10 years. It used to happen the baby was whipped away from the mother, put in the NICU, we don't even know the best medication buprenorphine is used, morphine, some use a mixture of opium, some use methadone, treated pharmacologically. The good news is that we found out that's probably the worst because we don't have any drug-drug interactions. Some of the ones that were used in bonding even 10 years ago just really was disruptive to the diet. Now we're trying to go to the eat, sleep, and console protocol and we're trying in most cases even if the infant is pivoting now to do rooming and withdrawal because beyond those medications infants do much better and mothers do much better if they're together rather than the infant being in the ICU. So here's how do you determine what to do if the infant can eat quickly or breastfeed, methadone has an inactive metabolite that's one of the differences but that's not really an issue increased right now because of interventions I don't think those medications are used in bonding and holding a low stimulation environment people know there's two medications hospitals are the least low stimulation environment we can imagine the antiviral we use to treat COVID do people know what those are? So that's tough and again the rooming in I can't even barely pronounce and I have to even use my phone to cue me can an infant sleep more than one hour? Which is one of the anti-retrovirals I just mentioned so the reason so it's really hugging and cooing just like we would do with any those of us who are parents or antivirals against COVID the retinovir is really in there to inhibiting the enzyme 3A4 so that you get higher levels in 10 minutes so the point is because retinovir the baby can just stay with the mother and the mother will work on this no other interventions or pharmacologic treatments if there doesn't seem to be again an issue increased non-pharmacologic treatments feeding on demand swaddling and holding low stimulation environment if any of you would be probably ordering and obviously if you also have a patient who's a pediatrician but I don't think good to know that right now we're suggesting we're going to send them to who are doing that so that's how we're seeing in HIV and I guess your role would be to coach your patients and if you have any patients who have untreated hepatitis C it's urgent to get them treated antivirals I don't know if people have any experience treating hep C is encouraged whether the patients are like a miracle drug very few side effects 8-12 weeks most people get 100% viral clearance a lot of medication getting into breast milk most common reason for leaving a liver transplant if you know that your patient is hepatitis C and we aren't treating enough of those patients so if you know that the patient has hepatitis C get them into a person who can treat them and actually in Washington State they're starting to train people who treat opioid use disorder also treat hepatitis C so much prescribing a medication really easy we've had formula shortages recently HIV or AIDS they should be vaccinated against the hepatitis are there any questions about pregnancy sexually transmitted infections and TB renal failure really shouldn't be a problem with both methadone and buprenorphine it's mainly excreted through the gut so we don't really have to change our dosing if they are on hemodialysis I have experience with patients on methadone getting hemodialysis and what the textbook said is no it's fine to use when our hemodialysis doesn't eliminate the methadone as well as it should it doesn't make a lot of sense if it's mostly excreted in the gut but my clinical experience was the patients told me after dialysis they started to feel withdrawal I don't have any experience sublocating for pregnancy sublocating for now is contraindicated I'm not an excipient in the sublocating it's fine to keep treating them and just listen to the patient and if the patient says I'm getting destabilized by the hemodialysis as I understand it the Braeburn product that hasn't come on the market in one week is probably okay in pregnancy compromised liver function like end stage cirrhosis certainly for those patients who are on methadone so the question is what if the patient is already on sublocated and we find out the patient is pregnant what do you do? stump the expert I haven't seen that what should we do people the patient is on a medication that has a teratogenic compound in it what would you do? what I would do is as much as I have a strong opinion thinking that sublocated is the top treatment for opioid use disorder in the fentanyl era I think that I would switch back to the sublingual buprenorphine Because I don't want to personally be responsible for a malformed fetus that's very unhappy situation. He was also caught diverting his buprenorphine in his residential program. So that kind of put me in a real, real heavy bind. And I really, what I've done, I've consulted with his medical team, pharmacist, and also I also reached out to interviewer, you know, MSL for the region, and I really, really wanted to get him self-locking. We are not seeing any rates of fetal malformations or anything like that. Supposedly, there's a risk for diversion. Supposedly, patients can dig out the medication. We haven't seen that. Right. As opposed to like a sublingual. So the far bigger risk is not treating opioid use disorder with medication, then you're going to have a lot of complications. So, yes, you're not going to be sued if you treat a pregnant person with buprenorphine and there is an adverse outcome. I mean, you could be sued, but you're not going to lose that lawsuit. And he seems to be working well. He didn't have any recurrence or relapse of opioid use until he passed away last month from GI bleed. I'm sorry, because the speakers are faced the wrong way. It's really hard to understand. So it might be some need to reduce the buprenorphine dose. How significant is that? And if you just have a female reproductive age, do they have to be on contraception? Do you supplicate? There's no requirement that they be on contraception. And I do not know the answer. Dr. Parks talked. If people don't mind hearing from a drug company representative, she really has the information. Because I don't know how. I suspect from that, you have to think about the pain management practices. And it's very, very rare to have a patient on buprenorphine. We're going to continue the buprenorphine and give full agonist. Opioids are on top of that. And I should say, if you have questions about that or you have patients that need to be managed, and especially if there's the controversy with your hospitalists, for those of you who have access to Up to Date, there's some really excellent articles in Up to Date about how to manage the acute and chronic pain in these patients. And usually, if there's any dissension about how to do it, most people do accept this in Up to Date as an authoritative source. And for pregnant women, we can use either buprenorphine or methadone. All benefits outweigh the risk. Very patient-specific. There is not a requirement to be on contraception that you asked us on. So I should have known all that. I didn't. But I'm glad we have another knowledgeable person here. And it's great to be supposedly teaching the course and learn something while you're teaching. My question goes along with what you've been talking about. Do you take the patient off the sublocate and never put back on and leave on the oral agent? Substance-induced psychiatric symptoms versus a primary psychiatric condition are identified. Well, again, easily on the first meeting with the patient. B, only after a full month of abstinence. C, without regard for family history. D, there is no specific period of time used to differentiate these. So, again, I don't have the answer to that. You all can decide. I mean, my inclination would be to not use a medication that has an excipient that, at least among animals, has been teratogenic. So, I mean, I'm generally pretty bold as a psychopharmacologist. Okay. You've got another case. I don't want to take undue risks. And just knowing how precious those neonates are, to have an adverse outcome is always tragic. A 19-year-old woman, university student, comes to you asking for treatment for heroin use. Someone who's about to have his second grandchild. Again, this case is probably a little outdated. Even though everything looks good and I have no reason to suspect there's going to be any problems. If they're saying that's heroin use, it's probably fentanyl. Everything's going to be perfect. We'll just read the case as it is, knowing that it might be a little different in 2023. Oh, one more. Okay. She has been using heroin intranasally for the past 15 months, daily for the last three months. She is now using about one gram daily. Some of her friends are now switching to intravenous use because it takes less heroin to keep from getting sick. She says she doesn't want to do that but may be forced to because she cannot keep paying the extra cost of nasal use. She has used all the money her parents gave her for school expenses to buy heroin. Her credit cards are maxed out and she has borrowed money from her friends. Until last semester, she had an overall B average. But this semester, she is not a policymaker and not an expert. When she doesn't use heroin, she has muscle aches, diarrhea, insomnia, and anxiety. She recognizes the symptoms as heroin withdrawal. I'm surprised because she thought she could not develop an addiction with nasal use. Because we don't have any definitive information. And I'm going to give you a little spoiler alert. Thanks to our knowledgeable person here that it's teratogenic in humans. Sometimes, I think, treatment isn't always carried out as would be optimal or expected. Premature, until we have more information. I don't think there's any answers to this. I will say, what is the diagnosis? So, again- We're seeing increasing use of sublocate. Maybe pretty obvious. We haven't heard any reports to volunteer to give their thinking on why neonate malformations. So, we don't have any evidence right now that it's a problem. There's certainly no reason why you, as an individual clinician, cannot give informed consent to your patients that that's a risk if they're going to be on sublocate. Oh, we have someone? Okay. We have a volunteer? Great. I was going to try and stumble through it myself. You're going to require them to use some form of birth control. This sounds like it's probably opioid use disorder because she's experiencing dysfunction in her life. She's having withdrawal. And she is having difficulty with trying to define the lines where she wants to cross and not being able to hold to them. Whatever you think is going to be best. Also, tolerance is developing because she's needing to use more and more to get the effect that she's looking for. She's spending a lot of time and money using the heroin. So, I think it's very clear she needs at least four or five of the DSM-5 criteria, maybe more from the prognosis, but it's a severe opioid use disorder. Does anyone have any questions about that? If she couldn't just stay sober as opposed to actually this has to be her only time of recovery being on the buprenorphine injection, then I think that's different. If they're still having options, I could be on buprenorphine and still be in recovery, or be on sublocate, buprenorphine long injectable, and still be in recovery if they're of a childbearing age, then I'll keep going with the buprenorphine sublingual. She's not going to have time to go to a methadone clinic, and I do believe that she's still young. She's already using Gram. The only six months of recovery he had was on the buprenorphine long injection medication. Now, it's a he, but if it's a she, then I would not advise her to come off of a buprenorphine injection, but I will make sure and document this as health to make sure that I counsel the patient about that. And I will involve their OBGYN and prenatal psychiatrists that were high risk OBGYNs. Okay, great. So we're going to move on to- Dr. Sexton, there's one more. Oh, I'm sorry. Just comparing the two medications pharmacologically, buprenorphine is a safer treatment than methadone. The area I'm least knowledgeable in is naltrexone. That would mean she'd have to do seven to ten days off of opioids. She's already staying. She's struggling with withdrawal. So unless we could put her in an inpatient unit, it would be hard to get her on the naltrexone. How about- Oh, I'm sending her to a residential treatment program where she's withdrawn from opioids and treated with behavioral interventions. Yes. What do people think about that as a- They want to have a baby. Yes. Treatment option. The whole point of getting patients on medications for opioid use disorder is to let them have high functional status and live their lives. We'd be taking her out of school for a period of time. They should live a full life with every activity available as anyone who doesn't have opioid use disorder. But also we know just taking people off of opioids, giving behavioral interventions, the risk of return to use is very high. Unfortunately, in our country right now, most young women who have this scenario are going to get sent to an inpatient residential program. They're probably going to be taken off fentanyl or heroin or whatever they're using and then sent home with no medication. Wrong, wrong, wrong. And that's why we're all here to tell the world how to do it right. Okay. Why not methadone? Well, I mean, methadone would be okay. We went over that a little bit a moment ago. So, number one, she would have to go to a program every day under observed dosing, which would be very inconvenient. And secondly, in my opinion, she has the potential to be exposed to people who have a long history of opioid use disorder who might pull her into that culture more. And I'd rather not see her exposed to that. But the main reason is obvious. The convenience of methamorphine is a safer medication. So, for our very first treatment try, I would try that versus going to methadone immediately. Anecdotally, I would say, with the wide availability of fentanyl, we haven't really mentioned this, but if you start someone on methadone in the Seattle area for awhile, it was difficult to get them on buprenorphine if you need to switch. If you start someone on buprenorphine, very easy to switch to methadone. So, in almost every case, unless the patient says, I want methadone, you have those two options, and they haven't been treated in the past. It makes sense to try buprenorphine first. So, we have to take advantage of that. So, the American Academy of Pediatrics recommends for adolescent patients who have opioid use disorder that they do get medications. We're always worried about giving medications to young people whose brains are still developing. Is it better than not getting medication? I believe it is. So, American Academy of Pediatrics, for a patient like this, if we have a nascent version of opioid use disorder, we can intervene early and get young people stabilized. We might avoid a whole lifetime of disability with severe chronic OUD. So, don't have hesitation about treating adolescents. Uh-oh, I'm up here telling you about how to treat youth. You're the expert. Over 16 years. So, as an expert, you think buprenorphine is the way to go. And maybe, even if we offered her some behavioral interventions, she would not avail herself of that. Probably, in most cases, that's going to be your first choice for adolescents. So, we'll talk about that. As we move through the case, we'll talk about that. There was one more. Go ahead. Just part of the treatment plan, she seems like she probably doesn't have a lot of education or knowledge around opioids. Adolescent who's only had opioid use disorder for a brief time, maybe naltrexone, where we're not exposing them to further opioids, might be a good choice. Great point. Thank you. Already saw, at least in adults, that if you can get patients on long-acting naltrexone, the outcomes are as good as with buprenorphine. Way in the back. I hasten to take the mic because I may speak too long. I had a couple of comments. Buprenorphine is probably going to be a very good first choice. Methadone is going to be much more challenging because, as you can see here, for people under 18, not only do they get parental consent, but they supposedly have to have a two-attempt set. I mean, we're required to do that piece. The other question about diagnoses, even though it's obvious that she's taken the opiates, it's been my experience because I also work in college, mental health. There's an overwhelming preponderance of trauma underpinning the start of using, in my clinical experience. Any psychiatric disorder that we're treating adolescents for, we'd like to involve the family and family therapy, if available and acceptable, is certainly the way to go. Using the full array of behavioral interventions that Dr. Renner talked about. Without something, it's going to be the trauma history because it's hard on both ends. So you're talking to three instructors who all work in the VA, and so PTSD is our bread and butter. But yeah, I mean, we as psychiatrists, it's one of the most common psychiatric diagnoses, and when you're talking about a substance use disorder, you have an enriched population for it. The good news is that the vast majority of medications that are now used for HIV infection don't have any drug-related reactions. Some of the ones that were used 20 and 10 years ago, the European efavirenz and the trauma here did have some interactions with methadone. And primarily the concern was that they would induce the metabolism of methadone. You happen to be a doctor, they're not going to talk to some stranger they don't know about. Some of the medications they need are going to be very abrupt. They do not seem to affect buprenorphine in the same way, even if they induce it in the form of an enzyme because, as we said, buprenorphine has an active metabolite. So if you metabolize it quickly, you're just going to get more of the active metabolite. Methadone has an inactive metabolite. I don't know if this has to follow up to this case scenario, but from the addiction circle, we try to make an emphasis that we don't require therapy or counseling as a buprenorphine treatment. Is it going to be beneficial? Yes. We talked about how PTSD is very often co-present, comorbid. There's other psychiatric illnesses. But getting them into treatment against their will, first of all, has no evidence-based benefits. And second, in harm reduction, what we believe is that we don't think about, oh, yeah, we just give them Suboxone and all of them are going to get better on their own. We're not saying that. What we are saying is that every patient wants to change and has the resource and capacity to change in their own timeline. And if they don't want to engage in any other therapy or component, I wouldn't force that on her. I will continue to talk to her about benefits of addressing those underlying psychiatric illnesses while I continue to provide buprenorphine or long injectable naltrexone or referring her to methadone. Okay. We've got another comment back there. That's something to think about if you have patients who are on methadone. Anecdotally, we've had a couple of patients who got transmitted. We couldn't stick with it. The idea of a combination of using the meth treatment, Suboxone, plus the therapy treatment. Actually, this is the main treatment modality in a lot of RTCs. My question is that a lot of study or issues that are comparing to the meth treatment alone and the meth plus the therapy, there's no difference. And if there's only therapy, no meth treatment, there's also no significant benefit per se or significant difference. And that's why in the recent years, the meth treatment has become more and more popular and has the evidence based on it. So, again, I'm not against using this combination of treatment. I think in that sense, the treatment of the therapy more possibly addressed the psychological stressor part of it as the comorbidity issues. And our thinking is that a lot of RTCs or other treatment facilities, that they will mandatory mandate that therapy is a requirement for a patient to receive meth treatment. But if that's the case, like, for example, if we say both therapy and meth treatment are evidence based and have benefits, then it can be vice versa. We never ask a patient that they need a mandate to have meth treatment to receive therapy. Why request them to have a mandate therapy to receive meth treatment? So that's just my personal opinion. I'll make a comment about that. I think you're essentially correct if I'm understanding you. And I think you're echoing what Dr. Parks said. We want to make sure patients get their medication and we don't want to drive them away by saying you must go to some treated treatment group or something like that. And so it is important to realize change. I actually have experience with patients on methadone who are getting hemodialysis. And what the textbook said is you probably need to reduce the methadone dose. Because we don't know if all the person doing is taking two minutes and prescribing buprenorphine and they're not getting any behavioral intervention, we don't know for sure that that's equal to getting behavioral intervention. I don't have any experience treating patients who are receiving buprenorphine on hemodialysis. Does anyone in the room have that experience? I think it's just fine to keep treating them. Just listen to the patient and take some of the rules. I'm getting destabilized by buprenorphine or dialysis. And yeah, if you can do that, probably going to other treatments is not going to add that much benefit. And I just wanted to mention that you probably noticed that we changed the terms. It used to be called medication-assisted therapy, MAT. But that has been utilized by some clinics to say, you know, this is medication-assisted. But the real therapy begins with the counseling and therapy and groups. So we changed the terminology to say, no, it's MOU, the medications for opioid use. And we changed the terminology to say, no, it's buprenorphine. So we changed the terminology to say, no, it's MOU, the medications for opioid use disorder. We're not going to call buprenorphine MAT, medication-assisted therapy, reflecting the change of thinking that we don't want to force therapy or behavioral intervention against the patient as a prerequisite to get on the buprenorphine treatment. Yeah, okay. So I did have a patient on end-stage liver disease and was on the tissue. Well, that is not, as you'll see, I think the cases are meant as a jumping-off point for discussion. So who cares? The complication was that he was also caught diverting his buprenorphine in his residential program. So that kind of put me in a real, real heavy bind. And what I've done, I've consulted with his medical team, pharmacists, and also I also reached out to an interviewer at MSL for the region, and I really, really wanted to get him on stop-block aid, buprenorphine injection, because it has, you know, supposedly there's a risk for diversion, supposedly a patient can take out the medication. I haven't seen that, as opposed to like a sublingual has virtually no risk for diversion. After talking with everyone, it just didn't make sense to get him on the buprenorphine injection. Even with the 100-milligram dose, it was going to be a risk for him to be at risk for over-sedation. I had put him on the 8 milligrams daily, and it seemed to be working well. We didn't have any recurrence or relapse of opioid use, but I think we see that most patients with OUD don't go to total abstinence immediately. So there might be some need to reduce short-term goal would be reduced use, safer use, protection from overdose, with consistent medication taking. Okay, so any other treatment goals? Also summarizing Dr. Park's talk, we want to try and make sure she doesn't have withdrawal symptoms. We want to try and reduce the cravings, and we want to try and make sure she stays on medication, because we know that right now this young woman is at very high risk for an overdose of buprenorphine, and if we can get her on medication, we might be saving her life. I should say, if you have questions about that or you have patients that need to be managed, we won't force any people to feel silly by stating the obvious. We're going to ask her to stop the heroin use for 12 to 24 hours. And if it's actually fentanyl use, maybe a little bit more. And we're going to probably coach her about how to do the home initiation. Or I guess in her case, it might be a dorm room initiation. And we're going to see if we can get her started on buprenorphine. And that is the initial treatment plan, so buprenorphine. This is over 16 years, so the clinic physician, again, this is a pretty old case. I don't know if this would really still happen now, but maybe the clinic physician gives her a prescription for a six-day supply of HIV infection at four milligrams per day. And she's told to participate in the clinic's relapse prevention workshop six days a week. And call back to schedule individual counseling at the clinic once a week. So our college mental health experts, he's shaking his head. Probably, that's not a treatment plan, I mean, this was not shared decision making. This is what you're going to do. So it's probably not a treatment plan that she's going to be willing to follow. And when we talked about the initiation, four milligrams is a great starting dose, but it's probably not going to stabilize someone within two or three days, which is our goal. So most likely, this young woman was underdosed. So she returns three days later, and she took eight milligrams per day over three days, which is probably a better dose, she might know better than the clinic physician. It was probably a better dose, but she didn't go to the relapse prevention. She didn't schedule individual counseling. And then she shows up and the counselor's not available to see her. So that youth, I mean, certainly a 19-year-old- We have a lot of flexibility in our VA programs, but at my program, when people, there's no wrong door. So when people come in, we are going to find a way, our staff is going to do whatever they need to do. They're not going to say, sorry, you're here the wrong day. So come back next week, knowing that it might be a little different in 2023. She has been using heroin intravenously for the past 15 months, daily for the last three months. She's now using about one gram daily. Some of her friends are now switching to intravenous use because it takes less heroin to keep from getting sick. She says she doesn't want to do that, but may be forced to, because she cannot keep pay and discuss how she's doing. And maybe we even need to go higher than the 12 milligrams. She has used all the money her parents gave her for school expenses to buy heroin. Her credit cards are maxed out, and she has borrowed money from her friends. Until last semester, she had an overall B average, but this semester, she is in academic difficulty. Okay, and she doesn't use heroin. She has muscle aches, diarrhea, insomnia, and anxiety. She recognizes the symptoms of heroin withdrawal, and was surprised because she thought she could not develop an addiction with nasal use. She has no prior history of drug treatment. And I'm going to give you a little spoiler alert. Except to have the office call her the next day to see how she is doing and discuss those issues. Sometimes treatment isn't always carried out as would be optimal. I can't answer this. I hope the rest of you can. Okay, so I don't think there's any answers to this. So what is the diagnosis? So again, maybe pretty obvious. Now I figured out how to go back. If anyone wants to volunteer to give their thinking on why you did or didn't make a diagnosis of opioid use disorder, feel free. I don't know if this is a badly worded question or badly worded answers. Okay, so. That was a question. Okay. We have someone? Okay, we have a volunteer. You want to know how often I was going to try and stumble through it myself. Perfect, if you could hold that question. Dr. Park is going to talk about that as soon as we're done with this case. This sounds like it's probably opioid use disorder. You're also interested in having a discussion. I don't know where we're going to get to that. She's having withdrawal. Again, so. And she is having difficulties like trying to find the lines of where she wants to cross and not be able to get to them. I actually earlier told you what I typically would do is I'd give Tolerance is developing because she's needing to use more and more to get the effect that she's looking for. My approach, I'd give the first prescription is money for using the heroin. Plus an extra eight milligrams for day one, and then two eight milligrams for the subsequent six days. Four or five is the DSM-5 criteria, maybe more for the diagnosis, moderate to severe opioid use disorder. Does anyone have any questions about that? To see if 16 milligrams is sufficient. So that could get the person to at least eight on the first day, and probably 16 year old woman who's been using opioids for 15 months and has never had any treatment. Sometimes that might be a little much, but usually that's sort of the sweet spot we want to get to. So that's what I would have done. I don't think we would have wanted to do things exactly the same because that didn't work out so well. Why do you think that's the best treatment for her? I think that it's the best treatment for her, she's 19, she's not going to have time to go to the methadone clinic. It might be good for the first couple days, but it might not be enough for the future. So those are my thoughts about it, and okay. She returns the following day at a time when neither the group nor the counselor is available. She's told she has to attend the relapse prevention workshop in order to get the medication, which we all agree is a bad idea, I believe. Okay, yeah, so you think it's not a bad idea, your recommendation is buprenorphine. I would agree with you that as a first treatment option, sending this young woman to an opioid treatment program where she'd have to go every day and where she'd be exposed to many, many older people and who have had opioid use disorder for a long time is not ideal. And again, we know that just comparing the two medications pharmacologically, buprenorphine is a safer treatment than methadone. Other things we could consider, we could consider naltrexone. So that's the end of the case. That would mean she'd have to do seven to ten days off of opioids, she's already saying she's struggling with withdrawal, so unless we could put her in an inpatient unit. Thank you all, this has been a great discussion. How about, you're obviously all thinking about this really clearly where she's withdrawn from opioids and treated with behavioral interventions. Last home stretch, thank you for your attention. I just, I think he just took a break, but I just wanted to appreciate what he said. That the patient came back, and when all else fails at my attempts at a period of time, I reflect back on their changed behavior. But also, we know just taking people off of opioids, giving behavioral interventions, the risk of return to use is very high, and so, unfortunately, in our country right now, most young women. We're going to talk about drug testing. Drug testing in an in-patient residential program, it's probably going to be taken off, fentanyl or heroin or whatever you're using, and then sent home with no medication. Wrong, wrong, wrong, and that's why we're all here to tell the world how to do it right. How I usually counsel my patients is that the drug testing, think of it like a visible speed camera with a warning sign that there's a speed camera at 300 feet ahead. Number one, she would have to go to a program every day under a certain dosing, which would be very inconvenient. And secondly, in my opinion, she has the potential to be exposed to people who have had a long history of opioid use disorder. Who might pull her into that culture more, and I'd rather not see her exposed to that. But the main reason is just the convenience of buprenorphine, and it's a safer medication. So for our very first treatment try, I would try that versus going to methadone immediately. Secondly, I mean, we haven't spoken about this, I'm sorry to interrupt you all, but let me speak implicitly. I have a thought, we haven't really mentioned this, but if you start someone on methadone, very, very difficult to get them on buprenorphine if you need to switch. If you start someone on buprenorphine, very easy to switch to methadone. So in almost every case, unless the patient says, I want methadone, you have those two options, and they haven't been treated in the past, it makes sense to try buprenorphine first. I think it's a good idea to see them in person and collect urine screens, and it'll guide you, your management for them. You can also talk about treatment planning. In terms of when I'm counseling the patients, I tell them exactly what substances I'm going to be testing for. It is very important to understand your measures, know your measures, know your measures, and know your measures, and know your measures that what you don't measure. If your urine testing does not include fentanyl, then it's probably not going to be an effective tool to measure the success or efficacy raised for what you should sort of treatment. So she's making the point that a lot of people who prescribe buprenorphine and naloxone just give medication, they don't have any behavioral interventions. It's also important to make sure that you're testing for buprenorphine. Is that ideal? No, is it better than not getting medication? I believe it is. So if they're testing negative for buprenorphine and your urine is not diluted to the point and they're on a decent dose, then you're worried about the potential diversion. Or if they have abused buprenorphine by taking a large amount when they picked up the prescription and they went off of buprenorphine by the time they came back to see you, then that is a concern. Ideally, lab testing should be random, observed, with a caveat. So when we say observed, we're not talking about DOT protocol for observation when you have to drop your pants to the knee level, do a 360 before the observer. We're going to get more history about the patient. Do you just work in college mental health? There are ways to do this trauma-informed way. Uh-oh, I'm up here telling you about how to treat youth and you're the expert. Especially if there's a concern. As an expert, you think buprenorphine is the way to go. You want to have the capacity for observed testing provided that the staff is educated and informed in a trauma-informed care. It should be convenient for the patient. It should be high quality. And maybe even if we offered her some behavioral interventions, she would not avail herself of that. Partly because ‑‑ Okay. That would be ideal. If your testing is going to routinely take four or five days to get back, then especially in the earlier part of the treatment, it may not be as useful as something that they can get back to you within the same day. There was one more good hand here. Great. Just part of the treatment plan, she seems like she probably doesn't have a lot of education or knowledge around opioids, the risks, what the risks of injection might be. She clearly didn't understand the risks of inflation. So actually providing psychoeducation could be a really important intervention. Great point. Thank you. I'm really happy with all the discussion we're having. So let's keep it up. If you all have the energy, there was a way in the back. So I tend to utilize the alcohol metabolite testing present in urine, which is ethyl glutamate and ethyl sulfate. I hasten to take the mic because I may speak too long. But I had a couple of comments around the comment about psychoeducation. I have a question. Doesn't that come with prescribing? Or if it doesn't, it should. So that should be an automatic. I mean, we're required to do that piece. The other question about diagnosing, even though it's obvious that she's taken her opiates, it's been my experience because I also work in college. I work in college mental health. There's an overwhelming preponderance of trauma underpinning the start of using in my clinical experience. And so we have to be, what can I say, professional and aggressive about, not aggressive, but make sure we ask those tough questions. And sometimes in this microwave world, if we leave out something, it's going to be the trauma. History, because it's hard on both ends. So you're talking to three instructors who all work in the VA, and so PTSD is our bread and butter. Yeah, I mean, we as psychiatrists, it's one of the most common psychiatric diagnoses, and when you're talking about substance use disorders you have an enriched population for, typically, I don't know about the youth, but they're like the younger adults that I've treated or the older adults I've treated. They often don't bring this up. They don't even know that the trauma is what's driving a lot of their symptomatology, so it's incumbent upon us to gently first build a therapeutic alliance and move forward and then gently explore that. Because they're not going to talk to, you happen to be a doctor, they're not going to talk to some stranger they don't know about some of the most frightening intimate details of their life. I mean, you obviously all know this, so I'm just spouting off the obvious. But anyway, thank you for bringing that up. If I make a comment about the counseling portion of the treatment that comes with it, opioid use disorder, I don't know if this has the follow-up to this case scenario, but we, from the addiction historical, we try to make an emphasis that you don't require therapy or counseling as a buprenorphine treatment. Is it going to be beneficial? Yes. We talked about how PTSD is very often co-present, comorbid. There's other psychiatric illnesses. But getting them into treatment against their will, first of all, has no evidence-based benefits. And second, in harm reduction, what we believe is that we're not, you know, we don't think about like, oh, yeah, we just give them Suboxone and all of them are going to get better on their own. No, we're not saying that. What we are saying is that every patient wants to change and has the resource and capacity to change in their own timeline. And if they don't want to engage in any other therapy or, you know, component, I wouldn't force that on her. But I will, you know, continue to talk to her about, you know, some benefits of addressing those underlying psychiatric illnesses while continuing to provide, you know, buprenorphine or, you know, long injectable naltrexone or refer them to a methadone clinic. Okay. We got another comment back here. For instance, this particular test that we have in our hospital is notorious for having high false positive rates. Well, I certainly am not against the idea of a combination of using the treatment, Suboxone Plus, the therapy treatment. Actually, this is the main treatment modality in a lot of RPCs. My question is that, you know, a lot of studies are issues that are comparing to the MAT treatment alone. And the MAT plus the therapy, there's no difference. And if there's only therapy, no MAT treatment, there's also no significant benefit per se or significant difference. And that's why, in the recent years, the MAT treatment has become more and more popular and has the evidence based on it. So, again, I'm not against using this combination of treatment. I think, in that sense, the treatment and the therapy more possibly address the psychological stressor part of it as the comorbidity issues. And our thinking is that a lot of RPCs or other treatment facilities, that they will mandatorily mandate that therapy is a requirement for patients to receive MAT treatment. But if that's the case, like, for example, if we say both therapy and MAT treatment are evidence based and have benefit, then it can be vice versa. We never ask a patient that they need a mandate to have MAT treatment to receive therapy. Why we request them to have a mandate therapy to receive MAT treatment. So that's just my personal opinion. Yeah. I'll make a comment about that. I think you're essentially correct, if I'm understanding you. And I think you're echoing what Dr. Park said. We want to make sure patients get their medication and we don't want to drive them away by saying you must go to some treatment or something like that. It is important to realize the randomized controlled trials that compared buprenorphine treatment with and without the behavioral interventions used high quality medical management as their comparator condition. So we don't know if all the person's doing is taking two minutes and prescribing buprenorphine and they're not getting any behavioral intervention, we don't know for sure that that's equal to getting behavioral intervention with high quality medical management. That's really important for all of you because you're psychiatrists who are trained to do therapy. And if anyone can do high quality medical management, you can do it in 15 minutes. You can prescribe the medication. You can find out what's going on in the person's life. You can support them in making some changes they might need to make, whether that's with their substance use or other areas using the motivational techniques that Dr. Renner talked about. And yeah, if you can do that, probably going to other treatment is not going to add that much benefit. And I just wanted to mention that you probably noticed that we changed the terms. It used to be called medication-assisted therapy, MAT, or MAT. But that has been utilized by some clinics to say this is medication-assisted, but the real therapy begins with the treatment counseling and therapy in groups. So we changed the terminology to say, no, it's MOUD, medications for opioid use disorder. We're not going to call buprenorphine MAT, medication-assisted therapy, reflecting the change of thinking that we don't want to force therapy or behavior intervention against the patient as a prerequisite to get on the buprenorphine treatment. Yeah, okay. Great. I don't think I need to talk about this more. That is not, as you'll see, I think the cases are meant as a jumping-off point for discussions of who cares, whether we even get to the rest of the case. But if we do get to it, you'll see that it still tends to be somewhat true. Some programs or even individual clinicians are requiring some kind of behavioral intervention involvement. And they are saying, if you don't do that, I'm not going to treat you. That's their right to do that, but we just don't agree that that's the right approach. So, yeah. I mean, personally, I think patients benefit a lot from therapy while they're on medication. I want to offer it to them and make sure that they know it's available. I'm not going to force them to do it. And so, yes, if it's beneficial in the long run after they are tapered off. So back to our patient, 19 years old, using heroin. We don't recommend a short-term treatment. I know some patients are coming here with buprenorphine. What are our treatment goals? Without any follow-up plan. And we really, really want to counsel against that. If I could negotiate with them, at least maybe one intermediate taper for six months would be better. We see that most patients with OED don't go to total abstinence immediately. So I think our short-term goal would be reduced use, safer use, protection from overdose, with consistent medication. Any other treatment goals? Well, we want to try and make sure she doesn't have withdrawal symptoms. We want to try and reduce the cravings. And we want to try and make sure she stays on medication. Because we know that right now this young woman is at very high risk for an overdose and even a fatal overdose. And if we can get her on medication, we might be saving her life. Okay, what's the initial treatment plan? Okay, we won't force people to feel silly by stating the obvious. We're going to ask her to stop the heroin use for 12 to 24 hours. And if it's actually fentanyl use, maybe a little bit more. We're going to probably coach her about how to do the home initiation, or I guess in her case, it might be a dorm room initiation. And we're going to see if we can get her started on buprenorphine. And that is the initial treatment plan. Now, what exactly are you talking about? So the clinic physician, again, this is a pretty old case. I don't know if this will really still happen now, but maybe. Look, it's great that you're not using fentanyl, and you're not using IV. But I want you to take a next step in recovery. Because right now, your brain is still telling you that the pain or discomfort or anxiety that you're dealing with is that you're not capable of dealing with them by yourself, and you have to take something extra on top of that. And if you're doing that, what you're doing is that you are, because one of the criticisms of buprenorphine is that it's just a disincentive of all you are. It's probably not a treatment plan that she is going to be willing to follow. And when we talked about the initiation, 4 milligrams is a great starting dose, but it's probably not going to stabilize someone within two or three days, which is our goal. So most likely, this young woman was underdosed. So she returns three days later, and she took 8 milligrams per day over three days, which is probably a better dose. She might feel better than the clinic physician. It's probably a better dose, but she then ran out. She didn't go to the relapse prevention. She didn't schedule individual counseling. And she shows up, and the counselor's not available to see her. So that, I mean, certainly, we have a lot of flexibility in our VA programs. But at my program, there's no wrong door. So when people come in, we are going to find a way. Our staff is going to do whatever they need to do to take care of that person that day. We're not going to say, oh, sorry, you're here the wrong day, so come back next week. So it didn't go so well. But I think they're supposed to say that. So what might have been done differently? Additional resources, SAMHSA website has wonderful resources. They also have PCSS has webinars available. They also have a mentor mentee program. If you're a champion to bring in people from your program to your hospital, to your clinic, and you'd like to get connected with an expert on the field, they can connect you to someone. And this is all in your PowerPoints. And I think that's the end. So thank you all for your attention. And Dr. Sexton, before we dismiss you, Dr. Sexton has a comment. Would I have not done anything differently? Oh, you're in drug testing. 8 milligram, 2 milligram screenings to take once a day. Or I would not do anything different except to have the office call her and see how she was doing. I think before the pandemic, a lot of people were going by once a month. I think the guideline for the patients on methadone was the minimum eight times a year. And for a lot of providers, when they're managing different patients, it just made sense to just like, oh, their prescriptions will be due, a month's supply with the refills. I'll just collect a urine screen every month when they come in. I don't know if this is a badly worded question or a badly worded answer. And this is the least, the world turning upside down. And that's when a lot of providers have realized that for most stable patients, they did well without frequent urine drug tests. Dr. Park is going to talk about that as soon as we're done with this case. But you're also interested in having a discussion. There's no legal requirement for patients to have a certain urine drug screening frequency on different urges. This is confusing. It's good to have a speak about it. But I actually earlier told you what I typically would do is I'd give, and again, this isn't the gospel, but I think once a year, if they have demonstrated their stability, and they're still connecting with you, plus maybe every six months, and they have done well, I don't think this is not a wrong thing to do. With a follow up phone call two or three days later, to see if 16 milligrams is sufficient. So that would get the person at least eight on the first day, and probably 16 on day two. If you can give me urine once a month, I'll live with that. I have a particular patient who has problems with the four-year-old male, problems with the opioid, alcohol, cocaine, and benzodiazepine use disorder, who has gone through multiple detoxes and regenerative programs, have failed out of conventional sublingual buprenorphine treatment. And she was only willing to do sublockate buprenorphine for the future. So those are my thoughts about it. And she returns the following day. At the time we did, when the counselor was available, she was told she has to attend the relapse prevention workshop in order to get the medication, which we all agree is a bad idea. I believe, or if you think it's not a bad idea, I've probably intimidated you into silence now. She does not return to the clinic for four weeks. When she does, she is smoking more heroin than before. She's working in a high-risk environment with greater access to opioids. What are you thinking would be a good plan at this point? College mental health people is this consistent with what you might expect to happen? It really depends on your comfort level, your capacity. You're not going to be, I think as long as you can demonstrate that you're monitoring them on a regular basis and your clinical impression of the patients justify that, then you cannot go wrong. We bring Dr. Park up to finish off the day. Thank you all. This has been a great discussion. And you're obviously all thinking about this really clearly and really deeply. So it's great to see that. How does that change anything in how you are doing? So her question is if the urine testing results will change any of my management. So actually, this question had come up at the last year's course, what someone asked was, if the standard of treatment for high-risk patients that you're going to continue to use a buprenorphine, either way, whether they're still using fentanyl or not, what utility does the urine drug test provide? And I think it absolutely changes my management. Even if I'm going to continue to reflect on their change behavior, if they're not doing well on, let's say, 16 milligrams, I'm not talking about going up on the dose or adding a group therapy. Not against his view, but for helping the provider, they would kind of consider that. So what I usually counsel, how I usually counsel my patients is that the system is fine. I don't want to go up because I'm visible. I'm off this medication. And with a warning sign, I don't need medication. I just want to pick up. But it gives me a chance to engage them in a conversation. Maybe the main job is not to catch them. And you want to make sure that there's no punitive measures with having a positive for substance use. It does change my management and my approach to monitor the treatment progress. And think of it as another therapeutic tool to discourage from their re-admissions. From your experience, is there any benefit when you do the GC-MS versus a urine versus an oil swab? So the question is, if it's beneficial to order GC-MS for a urine drug screen, this was not required during the COVID pandemic, implicitly. Because when they removed the in-person requirement for starting oral fluid testing, everyone by default was able to start buprenorphine medication without adulterating the specimen. Now that Ryan and Hayback is going to be back in action, but with a six-month grace period, the detection window is shorter. So oral fluid testing is essentially a serum test, but it's at lower concentration. So there's a higher false positive and false negative rate. And when I encounter the patients, I tell them exactly what substance I'm going to be testing for. It is very important to understand your measures, know your measures, know your measures, and know your measures, and just by that, then you can go with the oral fluid testing if your testing does not include fentanyl. It's probably not going to be an effective tool. The laboratory is a success. Or efficacy, the goal standards is still the urine specimen. Because it's also important to make sure that your testing for buprenorphine for all different is a scheduled premedication. It does have a clinical set of views. But for some patients, oral fluid testing is more convenient. And your urine, you're fairly sure that the urine is not diluted to the point and there are decent dose. Then you're worried about the potential diversion. Or if they have abused buprenorphine by taking a large amount by, you know, when they picked up the prescription and they went off of buprenorphine by the time they were taking it. That is gone by the end of 2022. Ideally, lab testing should be random. So DEA is saying that they're going to require everyone to have gone through an eight-hour training. When we say observe, we're not talking about DOT protocol for observation when you had our training. It's going to look like E-level to a 360. But this will satisfy it, you know. So, yes, and do this. There are ways to do this in a trauma-informed way. And most likely, you're going to be doing unobserved urine testing. But if you can, especially if there's a concern, if there's a case for concern, then you want to have the capacity for observed testing provided that the staff is educated and informed in a trauma-informed care. It should be convenient for the patient. It should be high quality. What I'm talking about is that if you can have access to proper lab testing, not just a point-of-care testing from urine cup that's being sold, then that'd be ideal. But from the way you are talking, if you're testing is going to routinely take four or five days to get back, especially in the earlier part of the treatment, it may not be as useful as something that they can get back to you within the same day. We were educated from the media. And fentanyl is very potent, very lethal. You test for a panel. The dealers in my hospital, we have a panel of nine. We don't test for PCP. We do test for amphetamine. We do test for benzodiazepine. We do test for oxycodone, methadone, buprenorphine. Especially when the new batch of fentanyl analogs come in, maybe they'll have an ethyl group of ethyl sulfate that's the alcohol metabolite. Urine alcohol test is not a reliable way to measure decent alcohol use. So they don't want to put a fatal amount of fentanyl to utilize in a daily alcohol metabolite testing in present-day urine, which is ethyl codeine and ethyl sulfate. Not to kill their customers. And we've seen that the human bodies have a remarkable capacity for building tolerance for fentanyl. I alluded to the confirmatory testing earlier today, if you remember. So initial test is going to be immunoassay. What that is that they have antibodies that are going to be designed to bind to the molecules of substances. So I'm trying to understand your question. So the fentanyl can come positively irritated if it's either yes or no, yes, it's present, yes, it's present on the cutoff, or not. When you order for confirmatory testing, you're actually ordering for GCMS, a gas chromatography mass spectrometer. The fentanyl will be positive on the urine. The mass spectrometer will actually count the number of molecules in the substances. It's going to be expensive, it's going to take a long time, but it's going to be very highly accurate, and it's going to be quantitative. Most times. From my perspective, it's all the time. So I live in the land of Breaking Bad. So just know that the immunoassay also has a higher false positive and higher false negative rate compared to GCMS. I think a common example would be a poppy seed product will be testing positive on the opiates. Now, I've used reference to a science episode where Elaine had a false test positive from poppy seed bagel on her opiate testing, and her boss is, you know, accusing her of, you know, being the drug dealer for Kramer. So I stopped using that reference about three years ago to medical students because I caught them doing... It's really a complicated question. The American Association for the Treatment of Opioid Dependence, which is the Guild for Opioid Treatment Program, is very much against allowing methadone to be reported from treatment programs to the FDA. Any patient can sign a consent to allow it to be released, but most patients are not going to sign a consent. So it's a double-edged sword. Because of the stigma, if we put it out on the PDAP, a lot of clinicians, if a patient comes to see them for something else, are going to go, oh, that patient's on methadone, that's a bad patient, I don't want that patient in my practice. On the other hand, if a patient's coming to see a clinician for something else, the clinician does not want her on methadone, they could be providing inadequate care. So I don't have the answer to it, but my guess is as long as the American Association for the Treatment of Opioid Dependence is against releasing it to PDMP, this will not see a PDAP. We'll get to you in a minute, but we'll see what we've got. It is so because, you know, Dr. Renner alluded to it, so fentanyl is currently on the, you know, that's going around. This is not a pharmaceutical-grade fentanyl. What the cartels have figured out and what the DEA has to do is that for them to put a particular substance under control, under their schedule, and to get them after legally, they have to know which substances they have, you know, they're talking about. So what the cartels in the clandestine labs are doing is that they're altering the fentanyl structures here and there, and we call them fentanyl analogs. And the, you know, a lot of these fentanyl analogs will have unpredictable half-life and the chemical structures. What that does is that some fentanyl analogs are not picked up or not getting picked up on fentanyl tests. So what our hospital did was to find a lab test that is able to pick up more fentanyl analogs, but at the cost of getting more high false positive rate. For instance, this particular test that we have in our hospital is notorious for having high false positive rate from, you know, from patients taking trials done. In that case, you want to send that for confirmation to make sure that it is indeed false positive or false negative. But my advice to you is to be cautious and not do that. So benzodiazepine, cannabinoids, amphetamines, cocaine metabolites. You have a patient that's failing. Methadone is failing, and sublingual buprenorphine. And you decide that the risk-benefit ratio is better to put them on sublutase. I mean, you can do that. And I think it would be a treatment of last resort at this point. Let's see. Let's see. Actually, yeah, ethyl gluconide, ethyl sulfate. Buprenorphine, fentanyl, oxycodone, methadone, they're not going to get picked up on morphine or opiates immunoassay. So it's very important to advocate for your hospital to have these panels as additional, especially if you're dealing with an opioid use disorder patient. Are they typically, do they typically qualify for either of the other treatments? So I talked about how testing for buprenorphine is important to make sure that they are adhering to the treatment and they're not, you know. I can take a first step at it. Diverting or abusing the medication. So I only heard the first part of the question. You will see as a contraindication to buprenorphine testing for buprenorphine. I mean, it's going to get the buprenorphine. And I told you that the confirmatory testing will give you quantitative results. A patient was caught diverting buprenorphine in front of our clinic a month ago. And he got charged with that. They're in a contraindication. But now the availability of buprenorphine injection, buprenorphine, that's not even going to phase us. From their buprenorphine to no buprenorphine. And the ratio will be, typically, just no buprenorphine will be greater than buprenorphine. And you're going to help me out here. Like, you got caught in front of my clinic. I cannot continue giving you buprenorphine. I know you need some. I know you need it for your recovery. But the least thing thing you could have done is to go out of, you know, get caught, you know, some miles away, you know? So I call for buprenorphine. If you let me do it, I'll give you self-blocking out. I will continue the treatment. But other than, like, with two non-related, or no buprenorphine, which reflects that they probably didn't take buprenorphine the entire iteration, they just took buprenorphine once before they came in, you know, to give you, so that can give you a clue about arranging a different protocol, making sure that you're mitigating the divergent risk. Yeah, I agree. I think that there are no real, the only contraindication would be, of course, you know, you want to have a reasonable, like, guidance towards, you know, even if you are collecting the unobserved urine, you do want to make sure, so what we have in our hospital is that we have, we designed the bathroom with a window to the back of the patient. So it's not in full observation of the patient's, you know, private area, but we can still, like, you know, make sure that they're not taking anything out of their back or pocket, or they're not taking, you know, water from the toilet. And if there's no buprenorphine, it's just pure buprenorphine, they may have put the buprenorphine medication into the water, so. And what kind of guidance would you? Point number nine, so the goals of buprenorphine maintenance treatment include. We are very fortunate to have effective medications for opioid use disorder, but we noticed that the methamphetamine use disorder is just as bad as opioid use disorder, and the difference is that we don't have effective treatment for methamphetamine use disorder. There's, you know, some consideration, you do wanna make sure that the AI is not, you know, in a, it's not a man who are having sex with men in that, you know, subgroup. Mirtazapine has been shown to be a little bit effective in treating patients in that subgroup who have a methamphetamine use disorder, and they, I think, expanded their, you know, trials to include patients who are not men who are having sex with men for methamphetamine use disorder. But there's not been a really, like, game-changing, miracle-making, like, buprenorphine methadone point number 10. Medically-managed withdrawal, formerly known as detox, without medications for opioid use disorder, in the treatment of opioid use disorder, either results in a long-term opioid abstinence, or is unlikely to result in long-term abstinence, or results in fewer ED uses, I suppose, in admissions, or always results in decreased overdose. Some studies show that it's beneficial, especially if it's, you know, like, if there's a comorbid ADHD. Other studies, it's not been, like, again, it has shown promise, it's not been a game-changer, and you worry about the abuse risk and diversion risk for, that comes with the methylphenidate or amphetamine assault. So, is, so there's no evidence that the buprenorphine or any other medication for opioid use disorder will be beneficial in the long run after they're tapered off. And among the more severe users who used methamphetamine more than 18 days per month, it had no effect, but in the less serious users, the propion compared to placebo did do a little better at reducing methamphetamine use, but yeah, there is no perfect medication. I will tell you, American Society of Addiction Medicine and American Academy of Addiction Psychiatry just collaborated on creating a treatment guideline for stimulant use disorders that will probably be out by the end of the year, so keep an eye out for that. Unfortunately, you're gonna see, there's not, besides contingency management, there's nothing that's, like, magic bullets, so we're all really struggling with that, and it's not just the methamphetamine. In Seattle, more than half of our patients with opioid use disorder also have methamphetamine use disorder, so it's a real scourge to start buprenorphine within a six-month period. Quick question. We're taking buprenorphine throughout the day whenever they have physical or emotional discomfort. So we started to talk about stimulants, so I thought that opioid and stimulant-like substance, so would you do anything differently about the kratom in terms of, you know, if you were to start the buprenorphine or do something else on top of it, or the dosing-wise or duration-wise? So, you know, the question about the kratom, and, you know, there are some, you know, studies that show that the buprenorphine was helpful to treat, and we talked about rapid titration of buprenorphine, and also, once we reached the stable fixed dose kratom, we want them to get off of, you know, opioids at the same time. When I counsel my patients, I, you know, we just, there are gonna be two patients for them to take PRNs, some PRN buprenorphine, and I'm telling them, so I'm not gonna stress this out, stress on this point in the acute phase.

buprenorphine

opioid use disorder

OUD

pharmacology

induction

maintenance

special populations

pregnant patients

adolescents

methadone

naltrexone

psychiatric disorders

counseling

pain management

fentanyl